rs71645952

Variant names:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001374258.1(BRAF):c.712-40T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00155 in 1,596,448 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0087 ( 19 hom., cov: 32)

Exomes 𝑓: 0.00079 ( 17 hom. )

Consequence

BRAF
NM_001374258.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.31

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

cardiofaciocutaneous syndrome
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
cardiofaciocutaneous syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P, Genomics England PanelApp
LEOPARD syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp
Noonan syndrome 7
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, Genomics England PanelApp
Noonan syndrome
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: ClinGen, Orphanet
anaplastic astrocytoma
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
Costello syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

BRAF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 7-140801600-A-T is Benign according to our data. Variant chr7-140801600-A-T is described in ClinVar as Benign. ClinVar VariationId is 259291.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00872 (1329/152342) while in subpopulation AFR AF = 0.0306 (1272/41574). AF 95% confidence interval is 0.0292. There are 19 homozygotes in GnomAd4. There are 624 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1329 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAF	NM_001374258.1 link	c.712-40T>A		intron_variant	Intron 5 of 19	ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6 link	c.712-40T>A		intron_variant	Intron 5 of 17	ENST00000646891.2	NP_004324.2	P15056

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2 link	c.712-40T>A		intron_variant	Intron 5 of 19		NM_001374258.1	ENSP00000496776.1		A0A2R8Y8E0
BRAF	ENST00000646891.2 link	c.712-40T>A		intron_variant	Intron 5 of 17		NM_004333.6	ENSP00000493543.1		P15056

Frequencies

GnomAD3 genomes

AF:

0.00874

AC:

1330

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0307

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00209

AC:

466

AN:

223160

AF XY:

0.00165

show subpopulations

Gnomad AFR exome

AF:

0.0316

Gnomad AMR exome

AF:

0.00109

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000821

Gnomad OTH exome

AF:

0.00107

GnomAD4 exome

AF:

0.000792

AC:

1144

AN:

1444106

Hom.:

Cov.:

AF XY:

0.000695

AC XY:

499

AN XY:

717738

show subpopulations

African (AFR)

AF:

0.0293

AC:

945

AN:

32300

American (AMR)

AF:

0.00117

AC:

AN:

43586

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25948

East Asian (EAS)

AF:

0.00

AC:

AN:

38200

South Asian (SAS)

AF:

0.0000357

AC:

AN:

83928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52724

Middle Eastern (MID)

AF:

0.00117

AC:

AN:

5144

European-Non Finnish (NFE)

AF:

0.0000417

AC:

AN:

1102636

Other (OTH)

AF:

0.00156

AC:

AN:

59640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

110

164

219

274

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00872

AC:

1329

AN:

152342

Hom.:

Cov.:

AF XY:

0.00838

AC XY:

624

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.0306

AC:

1272

AN:

41574

American (AMR)

AF:

0.00209

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68032

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

137

206

274

343

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00388

Hom.:

Bravo

AF:

0.00969

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over