7-140734590-A-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP7BP4
This summary comes from the ClinGen Evidence Repository: The c.*7T>C variant in the 3' UTR of BRAF is classified as likely benign because it occurs in a noncoding region, computational splice analyses do not predict an impact on splicing, and Alamut indicates that this nucleotide is not highly conserved (BP4, BP7). It has been identified in 0.0008791% (1/113754) of non-Finnish European chromosomes in gnomAD v2. RASopathy-specific ACMG/AMP Criteria applied (PMID:29493581): BP4, BP7. LINK:https://erepo.genome.network/evrepo/ui/classification/CA175333/MONDO:0021060/004
Frequency
Consequence
NM_004333.6 3_prime_UTR
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAF | NM_004333.6 | c.*7T>C | 3_prime_UTR_variant | 18/18 | ENST00000646891.2 | ||
BRAF | NM_001374258.1 | c.2401+27T>C | intron_variant | ENST00000644969.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000646891.2 | c.*7T>C | 3_prime_UTR_variant | 18/18 | NM_004333.6 | P4 | |||
BRAF | ENST00000644969.2 | c.2401+27T>C | intron_variant | NM_001374258.1 |
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151894Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251476Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135908
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461864Hom.: 0 Cov.: 33 AF XY: 0.0000234 AC XY: 17AN XY: 727234
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151894Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74168
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Jun 10, 2023 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 06, 2010 | The 2301+7T>C variant in BRAF occurs in the 3' UTR. This variant has not been pr eviously reported in the literature or been identified in our laboratory. This v ariant is not located in a region of high nucleotide conservation; however, this type of variant has not been previously reported as pathogenic in an individual with a Noonan spectrum disorder. The 3'UTR contains regulatory elements essenti al for the regulation and transport of the mRNA transcript, and variants in this region could result in dysregulation or disruption of these functions. While it is likely that this variant is benign, we cannot rule out that it may contribut e to the clinical features observed in this individual. - |
Noonan syndrome 7 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
LEOPARD syndrome 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
RASopathy Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen RASopathy Variant Curation Expert Panel | Jan 31, 2020 | The c.*7T>C variant in the 3' UTR of BRAF is classified as likely benign because it occurs in a noncoding region, computational splice analyses do not predict an impact on splicing, and Alamut indicates that this nucleotide is not highly conserved (BP4, BP7). It has been identified in 0.0008791% (1/113754) of non-Finnish European chromosomes in gnomAD v2. RASopathy-specific ACMG/AMP Criteria applied (PMID:29493581): BP4, BP7. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at