rs149702741
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_001374258.1(BRAF):c.1752T>C(p.Ile584=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,613,650 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
BRAF
NM_001374258.1 synonymous
NM_001374258.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.105
Genes affected
BRAF (HGNC:1097): (B-Raf proto-oncogene, serine/threonine kinase) This gene encodes a protein belonging to the RAF family of serine/threonine protein kinases. This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which affects cell division, differentiation, and secretion. Mutations in this gene, most commonly the V600E mutation, are the most frequently identified cancer-causing mutations in melanoma, and have been identified in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of lung. Mutations in this gene are also associated with cardiofaciocutaneous, Noonan, and Costello syndromes, which exhibit overlapping phenotypes. A pseudogene of this gene has been identified on the X chromosome. [provided by RefSeq, Aug 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 7-140776974-A-G is Benign according to our data. Variant chr7-140776974-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 44808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.105 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.000133 (194/1461368) while in subpopulation NFE AF= 0.000166 (184/1111654). AF 95% confidence interval is 0.000146. There are 1 homozygotes in gnomad4_exome. There are 97 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRAF | NM_001374258.1 | c.1752T>C | p.Ile584= | synonymous_variant | 14/20 | ENST00000644969.2 | |
BRAF | NM_004333.6 | c.1632T>C | p.Ile544= | synonymous_variant | 13/18 | ENST00000646891.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000644969.2 | c.1752T>C | p.Ile584= | synonymous_variant | 14/20 | NM_001374258.1 | |||
BRAF | ENST00000646891.2 | c.1632T>C | p.Ile544= | synonymous_variant | 13/18 | NM_004333.6 | P4 | ||
ENST00000700122.1 | n.502+2106A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000915 AC: 23AN: 251358Hom.: 0 AF XY: 0.000103 AC XY: 14AN XY: 135840
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GnomAD4 exome AF: 0.000133 AC: 194AN: 1461368Hom.: 1 Cov.: 32 AF XY: 0.000133 AC XY: 97AN XY: 727052
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GnomAD4 genome ? AF: 0.0000919 AC: 14AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74460
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 13, 2011 | Ile544Ile in exon 13 of BRAF: This variant has not been previously reported in t he literature; however, it is not expected to have clinical significance because it does not alter an amino acid residue and is not located near a splice juncti on. - |
BRAF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 17, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 29, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 04, 2022 | This alteration is classified as likely 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. - |
RASopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 05, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
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Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at