NM_001374258.1:c.36G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.36G>A (p.Ala12=) variant in the BRAF gene is 0.116% (14/7290) of Latino chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) LINK:https://erepo.genome.network/evrepo/ui/classification/CA281921/MONDO:0021060/004

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00033 ( 4 hom. )

Consequence

BRAF
NM_001374258.1 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:10

Conservation

PhyloP100: 0.0780

Publications

5 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
LEOPARD syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Noonan syndrome 7
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
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
Noonan syndrome-like disorder with loose anagen hair
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 -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374258.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRAF	NM_001374258.1	MANE Plus Clinical	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 20	NP_001361187.1	A0A2R8Y8E0
BRAF	NM_004333.6	MANE Select	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 18	NP_004324.2
BRAF	NM_001374244.1		c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 19	NP_001361173.1	A0A2U3TZI2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRAF	ENST00000644969.2	MANE Plus Clinical	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 20	ENSP00000496776.1	A0A2R8Y8E0
BRAF	ENST00000646891.2	MANE Select	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 18	ENSP00000493543.1	P15056
BRAF	ENST00000288602.11	TSL:1	c.36G>A	p.Ala12Ala	synonymous	Exon 1 of 19	ENSP00000288602.7	A0A2U3TZI2

Frequencies

GnomAD3 genomes

AF:

0.000172

AC:

AN:

150876

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00167

Gnomad FIN

AF:

0.0000956

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000207

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000726

AC:

AN:

107470

AF XY:

0.00102

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000276

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000194

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.000296

GnomAD4 exome

AF:

0.000335

AC:

383

AN:

1144176

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

255

AN XY:

574280

show subpopulations

African (AFR)

AF:

0.0000423

AC:

AN:

23666

American (AMR)

AF:

0.000392

AC:

AN:

33148

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22948

East Asian (EAS)

AF:

0.00

AC:

AN:

31838

South Asian (SAS)

AF:

0.00273

AC:

199

AN:

72880

European-Finnish (FIN)

AF:

0.0000301

AC:

AN:

33216

Middle Eastern (MID)

AF:

0.00138

AC:

AN:

3612

European-Non Finnish (NFE)

AF:

0.000169

AC:

148

AN:

873348

Other (OTH)

AF:

0.000323

AC:

AN:

49520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000172

AC:

AN:

150986

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

AN XY:

73766

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41182

American (AMR)

AF:

0.000197

AC:

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.00167

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.0000956

AC:

AN:

10460

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000207

AC:

AN:

67542

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.452

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000232

Hom.:

Bravo

AF:

0.0000680

ClinVar

ClinVar submissions

Significance:Benign

Revision:reviewed by expert panel

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

RASopathy (2)

BRAF-related disorder (1)

Cardiovascular phenotype (1)

LEOPARD syndrome 3 (1)

Noonan syndrome 7 (1)

Noonan syndrome and Noonan-related syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.95

PhyloP100

0.078

PromoterAI

0.037

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over