The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_002880.4(RAF1):c.119G>A (p.Arg40His)

CA201617

40585 (ClinVar)

Gene: RAF1
Condition: RASopathy
Inheritance Mode: Autosomal dominant inheritance
UUID: e3a025b8-32a2-4d0f-92e0-d44516304ddc
Approved on: 2024-09-17
Published on: 2024-10-01

HGVS expressions

NM_002880.4:c.119G>A
NM_002880.4(RAF1):c.119G>A (p.Arg40His)
NC_000003.12:g.12618603C>T
CM000665.2:g.12618603C>T
NC_000003.11:g.12660102C>T
CM000665.1:g.12660102C>T
NC_000003.10:g.12635102C>T
NG_007467.1:g.50577G>A
ENST00000416093.2:c.119G>A
ENST00000423275.6:c.119G>A
ENST00000491290.2:n.496G>A
ENST00000684903.1:c.119G>A
ENST00000685348.1:c.119G>A
ENST00000685437.1:c.119G>A
ENST00000685653.1:c.119G>A
ENST00000685738.1:c.119G>A
ENST00000685740.1:c.119G>A
ENST00000685959.1:c.119G>A
ENST00000686409.1:n.410G>A
ENST00000686455.1:n.482G>A
ENST00000686479.1:n.490G>A
ENST00000686762.1:c.119G>A
ENST00000687257.1:n.454G>A
ENST00000687326.1:c.119G>A
ENST00000687348.1:c.119G>A
ENST00000687923.1:c.119G>A
ENST00000687940.1:n.496G>A
ENST00000688269.1:n.418G>A
ENST00000688444.1:n.445G>A
ENST00000688543.1:c.119G>A
ENST00000688625.1:c.119G>A
ENST00000688753.1:c.119G>A
ENST00000688779.1:n.450G>A
ENST00000688803.1:n.449G>A
ENST00000689033.1:c.119G>A
ENST00000689097.1:c.119G>A
ENST00000689226.1:c.119G>A
ENST00000689389.1:c.119G>A
ENST00000689418.1:c.119G>A
ENST00000689481.1:c.119G>A
ENST00000689540.1:n.269G>A
ENST00000689876.1:c.119G>A
ENST00000689914.1:c.119G>A
ENST00000690397.1:c.119G>A
ENST00000690460.1:c.119G>A
ENST00000690625.1:n.422G>A
ENST00000691396.1:c.119G>A
ENST00000691718.1:c.119G>A
ENST00000691724.1:c.119G>A
ENST00000691779.1:c.119G>A
ENST00000691899.1:c.119G>A
ENST00000692093.1:c.119G>A
ENST00000692311.1:n.492G>A
ENST00000692558.1:n.484G>A
ENST00000692773.1:c.119G>A
ENST00000692777.1:n.447G>A
ENST00000692830.1:c.119G>A
ENST00000692959.1:c.119G>A
ENST00000693069.1:c.119G>A
ENST00000693312.1:c.-18-6541G>A
ENST00000693664.1:c.119G>A
ENST00000693705.1:c.119G>A
ENST00000251849.9:c.119G>A
ENST00000442415.7:c.119G>A
ENST00000251849.8:c.119G>A
ENST00000416093.1:c.119G>A
ENST00000423275.5:c.119G>A
ENST00000442415.6:c.119G>A
NM_002880.3:c.119G>A
NM_001354689.1:c.119G>A
NM_001354690.1:c.119G>A
NM_001354691.1:c.-12G>A
NM_001354692.1:c.-12G>A
NM_001354693.1:c.119G>A
NM_001354694.1:c.-12G>A
NM_001354695.1:c.-12G>A
NR_148940.1:n.534G>A
NR_148941.1:n.534G>A
NR_148942.1:n.534G>A
NM_001354689.3:c.119G>A
NM_001354690.2:c.119G>A
NM_001354691.2:c.-12G>A
NM_001354692.2:c.-12G>A
NM_001354693.2:c.119G>A
NM_001354694.2:c.-12G>A
NM_001354695.2:c.-12G>A
NR_148940.2:n.450G>A
NR_148941.2:n.450G>A
NR_148942.2:n.450G>A
NM_001354690.3:c.119G>A
NM_001354691.3:c.-12G>A
NM_001354692.3:c.-12G>A
NM_001354693.3:c.119G>A
NM_001354694.3:c.-12G>A
NM_001354695.3:c.-12G>A
NR_148940.3:n.450G>A
NR_148941.3:n.450G>A
NR_148942.3:n.450G>A
More

Benign

Met criteria codes 5
BS4 BP5 BP4 BS2_Supporting BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RAF1 Version 2.1.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
RASopathy VCEP
The c.119G>A variant in the RAF1 gene is a missense variant predicted to cause substitution of arginine by histidine at amino acid 40 (p.Arg40His). The filtering allele frequency of this variant is 0.5265% for Admixed American chromosomes in gnomAD v4, 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 computational predictor REVEL gives a score of 0.281, which is below the threshold of 0.3 and does not predict a damaging effect on RAF1 function (BP4). This variant has been identified in a patient with an alternate molecular basis for disease and did not segregate with disease in affected family members (BP5, BS4; GeneDx internal data; GTR ID: 26957; SCV000171283.11). Additionally this variant was identified in multiple healthy individuals (BS2_P, Eurofins, SCV000227278.5; Illumina, SCV000440638.3; Ambry Genetics, SCV000736788.4). In summary, this variant meets criteria to be classified as benign for autosomal dominant RASopathies based on the ACMG/AMP criteria applied, as specified by the ClinGen RASopathy Variant Curation Expert Panel: BA1, BS4, BS2_supporting, BP4, BP5 (Specification Version 2.1, 9/17/2024)
Met criteria codes
BS4
The variant did not segregate with disease in affected family members (BS4; GeneDx internal data; GTR ID: 26957; ClinVar SCV000171283.11; SCV000227278.4)
BP5
This variant has been identified in a patient with an alternate molecular basis for disease and did not segregate with disease in affected family members (BP5, BS4; GeneDx internal data; GTR ID: 26957; SCV000171283.11)
BP4
The computational predictor REVEL gives a score of 0.281
BS2_Supporting
This variant was identified in multiple healthy individuals (BS2_P, Eurofins, SCV000227278.5; Illumina, SCV000440638.3; Ambry Genetics, SCV000736788.4)
BA1
The filtering allele frequency of the c.119G>A (p.Arg40His) variant in the RAF1 gene is 0.5265% for Admixed American chromosomes in gnomAD v4, 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).
Curation History
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