Variant: NM_002880.3(RAF1):c.-267G>A

CA181005

40575 (ClinVar)

Gene: RAF1

Condition: RASopathy

Inheritance Mode: Autosomal dominant inheritance

UUID: 8ca8203f-7106-4509-94f8-6bfbd5481879

HGVS expressions

NM_002880.3:c.-267G>A
NM_002880.3(RAF1):c.-267G>A
NC_000003.12:g.12664053C>T
CM000665.2:g.12664053C>T
NC_000003.11:g.12705552C>T
CM000665.1:g.12705552C>T
NC_000003.10:g.12680552C>T
NG_007467.1:g.5127G>A
NM_001354689.1:c.-267G>A
NM_001354691.1:c.-490G>A
NM_001354692.1:c.-397G>A
NM_001354693.1:c.-267G>A
NM_001354694.1:c.-397G>A
NM_001354695.1:c.-397G>A
NR_148940.1:n.149G>A
NR_148941.1:n.149G>A
NR_148942.1:n.149G>A
ENST00000251849.8:c.-267G>A
ENST00000416093.1:c.-267G>A
ENST00000423275.5:c.-267G>A
ENST00000442415.6:c.-267G>A

Benign

• Met criteria codes: BP4 BP5 BP7 BA1

Expert Panel

RASopathy VCEP

Criteria Specification Information

Evidence submitted by expert panel

RASopathy VCEP

The c.-267G>A variant was identified in the RAF1 gene. The filtering allele frequency for the c.-267G>A is 6.32% for African chromosomes in gnomAD (68/8706 with 95% CI) (https://gnomad.broadinstitute.org/), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert panel for autosomal dominant RASopathy variants (BA1). The variant has also been identified in a patient with an alternate molecular basis for disease (BP5; Laboratory for Molecular Medicine internal data). In summary, the c.-267G>A variant meets criteria to be classified as benign. RASopathy-specific ACMG/AMP criteria applied (PMID:29493581): BA1, BP5.

Met criteria codes

• BP4: Evolutionarily conserved with no predicted splicing impact
• BP5: Patient observed with pathogenic variant c.922A>G (p.Asn308Asp) in PTPN1 (Laboratory for Molecular Medicine internal data).
• BP7: Silent variant with no predicted splicing impact
• BA1: Present in 68/8706 (6.32% MAF 95% CI) African alleles in gnomAD

Approved on: 2019-07-25

Published on: 2019-12-03