rs3730296
Variant summary
Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1
This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.1755A>G (p.Val585=) variant in the RAF1 gene is 6.222% (690/10404) of African chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) LINK:https://erepo.genome.network/evrepo/ui/classification/CA134709/MONDO:0021060/004
Frequency
Consequence
NM_002880.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Benign. The variant received -8 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0194 AC: 2955AN: 152190Hom.: 94 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.00505 AC: 1270AN: 251380 AF XY: 0.00376 show subpopulations
GnomAD4 exome AF: 0.00197 AC: 2880AN: 1461868Hom.: 86 Cov.: 31 AF XY: 0.00160 AC XY: 1161AN XY: 727236 show subpopulations
GnomAD4 genome AF: 0.0195 AC: 2968AN: 152308Hom.: 95 Cov.: 32 AF XY: 0.0195 AC XY: 1450AN XY: 74482 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:4
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not provided Benign:3
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RASopathy Benign:3
Variant classified using ACMG guidelines -
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The filtering allele frequency of the c.1755A>G (p.Val585=) variant in the RAF1 gene is 6.222% (690/10404) of African chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) -
LEOPARD syndrome 2 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Cardiovascular phenotype Benign:1
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Noonan syndrome and Noonan-related syndrome Benign:1
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Noonan syndrome 5 Benign:1
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at