7-140800335-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001374258.1(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_001374258.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0360

Publications

8 publications found

Variant links:

COSMIC-nc: COSV56078567

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 -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 VariationId 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 rank	MANE	Protein	UniProt
BRAF	NM_001374258.1 link	c.980+27G>A		intron_variant	Intron 7 of 19	ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6 link	c.980+27G>A		intron_variant	Intron 7 of 17	ENST00000646891.2	NP_004324.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2 link	c.980+27G>A		intron_variant	Intron 7 of 19		NM_001374258.1	ENSP00000496776.1
BRAF	ENST00000646891.2 link	c.980+27G>A		intron_variant	Intron 7 of 17		NM_004333.6	ENSP00000493543.1

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

GnomAD2 exomes

AF:

0.0700

AC:

17587

AN:

251312

AF XY:

0.0760

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 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

African (AFR)

AF:

0.0180

AC:

601

AN:

33466

American (AMR)

AF:

0.0352

AC:

1576

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

2800

AN:

26128

East Asian (EAS)

AF:

0.0834

AC:

3309

AN:

39692

South Asian (SAS)

AF:

0.113

AC:

9763

AN:

86230

European-Finnish (FIN)

AF:

0.0591

AC:

3154

AN:

53376

Middle Eastern (MID)

AF:

0.123

AC:

704

AN:

5702

European-Non Finnish (NFE)

AF:

0.0708

AC:

78669

AN:

1111762

Other (OTH)

AF:

0.0737

AC:

4449

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

5213

10426

15638

20851

26064

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2988

5976

8964

11952

14940

<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:

0.0564

AC:

8588

AN:

152198

Hom.:

291

Cov.:

AF XY:

0.0572

AC XY:

4253

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.0219

AC:

909

AN:

41532

American (AMR)

AF:

0.0530

AC:

811

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.104

AC:

360

AN:

3468

East Asian (EAS)

AF:

0.0835

AC:

433

AN:

5184

South Asian (SAS)

AF:

0.114

AC:

547

AN:

4818

European-Finnish (FIN)

AF:

0.0587

AC:

621

AN:

10584

Middle Eastern (MID)

AF:

0.109

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0693

AC:

4714

AN:

68000

Other (OTH)

AF:

0.0602

AC:

127

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

426

851

1277

1702

2128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

224

336

448

560

<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:

0.0511

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.83

CADD

Benign

7.5

(source)

DANN

Benign

0.63

PhyloP100

-0.036

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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