Variant 7-140785890-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001374258.1(BRAF):c.1178-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 397,150 control chromosomes in the GnomAD database, including 15,407 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 10783 hom., cov: 32)

Exomes 𝑓: 0.17 ( 4624 hom. )

Consequence

BRAF
NM_001374258.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.78

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 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.1178-82G>A		intron_variant		ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6 linkuse as main transcript	c.1177+1658G>A		intron_variant		ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	Effect	MANE	Protein	Appris
BRAF	ENST00000644969.2 linkuse as main transcript	c.1178-82G>A	intron_variant	NM_001374258.1	ENSP00000496776
BRAF	ENST00000646891.2 linkuse as main transcript	c.1177+1658G>A	intron_variant	NM_004333.6	ENSP00000493543	P4
	ENST00000700122.1 linkuse as main transcript	n.503-8395C>T	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

45231

AN:

151856

Hom.:

10734

Cov.:

show subpopulations

Gnomad AFR

AF:

0.664

Gnomad AMI

AF:

0.104

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.309

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.309

Gnomad NFE

AF:

0.142

Gnomad OTH

AF:

0.268

GnomAD4 exome

AF:

0.169

AC:

41347

AN:

245176

Hom.:

4624

AF XY:

0.165

AC XY:

20561

AN XY:

124284

show subpopulations

Gnomad4 AFR exome

AF:

0.650

Gnomad4 AMR exome

AF:

0.152

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.138

Gnomad4 SAS exome

AF:

0.305

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.147

Gnomad4 OTH exome

AF:

0.211

GnomAD4 genome

AF:

0.298

AC:

45329

AN:

151974

Hom.:

10783

Cov.:

AF XY:

0.296

AC XY:

21981

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.664

Gnomad4 AMR

AF:

0.180

Gnomad4 ASJ

AF:

0.198

Gnomad4 EAS

AF:

0.173

Gnomad4 SAS

AF:

0.308

Gnomad4 FIN

AF:

0.153

Gnomad4 NFE

AF:

0.142

Gnomad4 OTH

AF:

0.268

Alfa

AF:

0.187

Hom.:

1890

Bravo

AF:

0.312

Asia WGS

AF:

0.277

AC:

963

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over