Variant rs62487918 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004333.6(BRAF):c.1518-48C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 1,592,052 control chromosomes in the GnomAD database, including 4,469 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 289 hom., cov: 32)

Exomes 𝑓: 0.072 ( 4180 hom. )

Consequence

BRAF
NM_004333.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0310

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-140777136-G-A is Benign according to our data. Variant chr7-140777136-G-A is described in ClinVar as [Benign]. Clinvar id is 40378.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRAF	NM_001374258.1 linkuse as main transcript	c.1638-48C>T		intron_variant		ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6 linkuse as main transcript	c.1518-48C>T		intron_variant		ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	Effect	MANE	Protein	Appris
BRAF	ENST00000644969.2 linkuse as main transcript	c.1638-48C>T	intron_variant	NM_001374258.1	ENSP00000496776
BRAF	ENST00000646891.2 linkuse as main transcript	c.1518-48C>T	intron_variant	NM_004333.6	ENSP00000493543	P4
	ENST00000700122.1 linkuse as main transcript	n.502+2268G>A	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0568

AC:

8625

AN:

151816

Hom.:

288

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.0531

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0848

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0590

Gnomad MID

AF:

0.115

Gnomad NFE

AF:

0.0694

Gnomad OTH

AF:

0.0610

GnomAD3 exomes

AF:

0.0703

AC:

17371

AN:

247080

Hom.:

803

AF XY:

0.0761

AC XY:

10166

AN XY:

133550

show subpopulations

Gnomad AFR exome

AF:

0.0203

Gnomad AMR exome

AF:

0.0317

Gnomad ASJ exome

AF:

0.108

Gnomad EAS exome

AF:

0.0959

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0624

Gnomad NFE exome

AF:

0.0718

Gnomad OTH exome

AF:

0.0717

GnomAD4 exome

AF:

0.0718

AC:

103337

AN:

1440134

Hom.:

4180

Cov.:

AF XY:

0.0740

AC XY:

53110

AN XY:

717382

show subpopulations

Gnomad4 AFR exome

AF:

0.0185

Gnomad4 AMR exome

AF:

0.0352

Gnomad4 ASJ exome

AF:

0.107

Gnomad4 EAS exome

AF:

0.0834

Gnomad4 SAS exome

AF:

0.113

Gnomad4 FIN exome

AF:

0.0592

Gnomad4 NFE exome

AF:

0.0706

Gnomad4 OTH exome

AF:

0.0741

GnomAD4 genome

AF:

0.0568

AC:

8624

AN:

151918

Hom.:

289

Cov.:

AF XY:

0.0576

AC XY:

4273

AN XY:

74216

show subpopulations

Gnomad4 AFR

AF:

0.0226

Gnomad4 AMR

AF:

0.0531

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.0847

Gnomad4 SAS

AF:

0.115

Gnomad4 FIN

AF:

0.0590

Gnomad4 NFE

AF:

0.0694

Gnomad4 OTH

AF:

0.0604

Alfa

AF:

0.0677

Hom.:

Bravo

AF:

0.0531

Asia WGS

AF:

0.0930

AC:

325

AN:

3478

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

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

-0.67

CADD

Benign

7.6

DANN

Benign

0.83

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