Variant 7-140800335-C-T 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.980+27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0704 in 1,613,628 control chromosomes in the GnomAD database, including 4,526 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.056 ( 291 hom., cov: 32)

Exomes 𝑓: 0.072 ( 4235 hom. )

Consequence

BRAF
NM_004333.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0360

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:

BRAF (HGNC:):

BRAF 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=-0.83).

BP6

Variant 7-140800335-C-T is Benign according to our data. Variant chr7-140800335-C-T is described in ClinVar as [Benign]. Clinvar id is 40354.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.106 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.980+27G>A		intron_variant		ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6 linkuse as main transcript	c.980+27G>A		intron_variant		ENST00000646891.2	NP_004324.2	P15056

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2 linkuse as main transcript	c.980+27G>A		intron_variant			NM_001374258.1	ENSP00000496776.1		A0A2R8Y8E0
BRAF	ENST00000646891.2 linkuse as main transcript	c.980+27G>A		intron_variant			NM_004333.6	ENSP00000493543.1		P15056

Frequencies

GnomAD3 genomes

AF:

0.0565

AC:

8589

AN:

152080

Hom.:

290

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0219

Gnomad AMI

AF:

0.0374

Gnomad AMR

AF:

0.0531

Gnomad ASJ

AF:

0.104

Gnomad EAS

AF:

0.0837

Gnomad SAS

AF:

0.113

Gnomad FIN

AF:

0.0587

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.0693

Gnomad OTH

AF:

0.0608

GnomAD3 exomes

AF:

0.0700

AC:

17587

AN:

251312

Hom.:

823

AF XY:

0.0760

AC XY:

10318

AN XY:

135826

show subpopulations

Gnomad AFR exome

AF:

0.0194

Gnomad AMR exome

AF:

0.0317

Gnomad ASJ exome

AF:

0.107

Gnomad EAS exome

AF:

0.0948

Gnomad SAS exome

AF:

0.112

Gnomad FIN exome

AF:

0.0622

Gnomad NFE exome

AF:

0.0717

Gnomad OTH exome

AF:

0.0708

GnomAD4 exome

AF:

0.0719

AC:

105025

AN:

1461430

Hom.:

4235

Cov.:

AF XY:

0.0741

AC XY:

53900

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.0180

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:

0.0591

Gnomad4 NFE exome

AF:

0.0708

Gnomad4 OTH exome

AF:

0.0737

GnomAD4 genome

AF:

0.0564

AC:

8588

AN:

152198

Hom.:

291

Cov.:

AF XY:

0.0572

AC XY:

4253

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0219

Gnomad4 AMR

AF:

0.0530

Gnomad4 ASJ

AF:

0.104

Gnomad4 EAS

AF:

0.0835

Gnomad4 SAS

AF:

0.114

Gnomad4 FIN

AF:

0.0587

Gnomad4 NFE

AF:

0.0693

Gnomad4 OTH

AF:

0.0602

Alfa

AF:

0.0511

Hom.:

Bravo

AF:

0.0529

Asia WGS

AF:

0.0900

AC:

315

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

-0.83

CADD

Benign

7.5

DANN

Benign

0.63

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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