Variant chr7-140777956-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004333.6(BRAF):c.1517+35G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,598,902 control chromosomes in the GnomAD database, including 385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 26 hom., cov: 32)

Exomes 𝑓: 0.019 ( 359 hom. )

Consequence

BRAF
NM_004333.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.201

Variant links:

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]

BRAF links:

ENSG00000289788 (HGNC:):

ENSG00000289788 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 7-140777956-C-G is Benign according to our data. Variant chr7-140777956-C-G is described in ClinVar as [Benign]. Clinvar id is 40376.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0147 (2241/152270) while in subpopulation AMR AF= 0.0247 (377/15290). AF 95% confidence interval is 0.0226. There are 26 homozygotes in gnomad4. There are 1064 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2241 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAF	NM_001374258.1 link	c.1637+35G>C		intron_variant		ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6 link	c.1517+35G>C		intron_variant		ENST00000646891.2	NP_004324.2	P15056

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2 link	c.1637+35G>C		intron_variant			NM_001374258.1	ENSP00000496776.1		A0A2R8Y8E0
BRAF	ENST00000646891.2 link	c.1517+35G>C		intron_variant			NM_004333.6	ENSP00000493543.1		P15056

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2242

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00432

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0247

Gnomad ASJ

AF:

0.0363

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0213

Gnomad OTH

AF:

0.0220

GnomAD3 exomes

AF:

0.0138

AC:

3458

AN:

249992

Hom.:

AF XY:

0.0143

AC XY:

1926

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.00322

Gnomad AMR exome

AF:

0.0118

Gnomad ASJ exome

AF:

0.0375

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.00308

Gnomad FIN exome

AF:

0.00363

Gnomad NFE exome

AF:

0.0207

Gnomad OTH exome

AF:

0.0178

GnomAD4 exome

AF:

0.0189

AC:

27379

AN:

1446632

Hom.:

359

Cov.:

AF XY:

0.0186

AC XY:

13372

AN XY:

720664

show subpopulations

Gnomad4 AFR exome

AF:

0.00281

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0372

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00309

Gnomad4 FIN exome

AF:

0.00374

Gnomad4 NFE exome

AF:

0.0218

Gnomad4 OTH exome

AF:

0.0207

GnomAD4 genome

AF:

0.0147

AC:

2241

AN:

152270

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1064

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00431

Gnomad4 AMR

AF:

0.0247

Gnomad4 ASJ

AF:

0.0363

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.0213

Gnomad4 OTH

AF:

0.0227

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0155

Asia WGS

AF:

0.00231

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

2.6

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over