rs369182143
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_004333.6(BRAF):c.723G>A(p.Thr241Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,612,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000058 ( 0 hom. )
Consequence
BRAF
NM_004333.6 synonymous
NM_004333.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.550
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=-0.34).
BP6
Variant 7-140801549-C-T is Benign according to our data. Variant chr7-140801549-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 417224.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.55 with no splicing effect.
BS1
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000131 (20/152144) while in subpopulation AMR AF= 0.000327 (5/15284). AF 95% confidence interval is 0.000129. There are 0 homozygotes in gnomad4. There are 8 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BRAF | NM_001374258.1 | c.723G>A | p.Thr241Thr | synonymous_variant | 6/20 | ENST00000644969.2 | NP_001361187.1 | |
BRAF | NM_004333.6 | c.723G>A | p.Thr241Thr | synonymous_variant | 6/18 | ENST00000646891.2 | NP_004324.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BRAF | ENST00000644969.2 | c.723G>A | p.Thr241Thr | synonymous_variant | 6/20 | NM_001374258.1 | ENSP00000496776.1 | |||
BRAF | ENST00000646891.2 | c.723G>A | p.Thr241Thr | synonymous_variant | 6/18 | NM_004333.6 | ENSP00000493543.1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000723 AC: 18AN: 248850Hom.: 0 AF XY: 0.0000817 AC XY: 11AN XY: 134634
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GnomAD4 exome AF: 0.0000575 AC: 84AN: 1460432Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 726490
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GnomAD4 genome AF: 0.000131 AC: 20AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74314
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 06, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 26, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2024 | BRAF: BP4, BP7 - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 13, 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 | Labcorp Genetics (formerly Invitae), Labcorp | Dec 30, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at