7-140734210-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_004333.6(BRAF):c.*387G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,103,716 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0090 ( 29 hom., cov: 32)

Exomes 𝑓: 0.00084 ( 11 hom. )

Consequence

BRAF
NM_004333.6 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.867

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 7-140734210-C-T is Benign according to our data. Variant chr7-140734210-C-T is described in ClinVar as [Benign]. Clinvar id is 359041.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00904 (1377/152286) while in subpopulation AFR AF= 0.0316 (1312/41544). AF 95% confidence interval is 0.0302. There are 29 homozygotes in gnomad4. There are 646 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 1377 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRAF	NM_004333.6 linkuse as main transcript	c.*387G>A		3_prime_UTR_variant	18/18	ENST00000646891.2
BRAF	NM_001374258.1 linkuse as main transcript	c.2401+407G>A		intron_variant		ENST00000644969.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRAF	ENST00000646891.2 linkuse as main transcript	c.*387G>A		3_prime_UTR_variant	18/18		NM_004333.6	P4
BRAF	ENST00000644969.2 linkuse as main transcript	c.2401+407G>A		intron_variant			NM_001374258.1

Frequencies

GnomAD3 genomes

AF:

0.00905

AC:

1377

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0317

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.000844

AC:

803

AN:

951430

Hom.:

Cov.:

AF XY:

0.000735

AC XY:

325

AN XY:

441894

show subpopulations

Gnomad4 AFR exome

AF:

0.0314

Gnomad4 AMR exome

AF:

0.00394

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000932

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000708

Gnomad4 OTH exome

AF:

0.00153

GnomAD4 genome

AF:

0.00904

AC:

1377

AN:

152286

Hom.:

Cov.:

AF XY:

0.00867

AC XY:

646

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0316

Gnomad4 AMR

AF:

0.00262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.00720

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Noonan syndrome 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

LEOPARD syndrome 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

Cadd

Benign

3.5

Dann

Benign

0.71

Splicing

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