chr7-140808351-CAA-C

Variant names:

Variant summary

Our verdict is . The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_004333.6(BRAF):c.609-291_609-290delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 192,102 control chromosomes in the GnomAD database, including 57 homozygotes. Variant has been reported in ClinVar as Benign (★). The gene BRAF is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.052 ( 57 hom., cov: 21)

Exomes 𝑓: 0.11 ( 0 hom. )

Consequence

BRAF
NM_004333.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.450

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), Genomics England PanelApp, G2P, Ambry Genetics, PanelApp Australia
LEOPARD syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, PanelApp Australia
Noonan syndrome 7
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, G2P, Ambry Genetics, PanelApp Australia
large congenital melanocytic nevus
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
Noonan syndrome
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
Noonan syndrome with multiple lentigines
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
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

new If you want to explore the variant's impact on the transcript NM_004333.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for BRAF are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 7-140808351-CAA-C is Benign according to our data. Variant chr7-140808351-CAA-C is described in ClinVar as Benign. ClinVar VariationId is 1280023.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004333.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRAF	NM_001374258.1	MANE Plus Clinical	c.609-291_609-290delTT	intron	N/A	NP_001361187.1	A0A2R8Y8E0
BRAF	NM_004333.6	MANE Select	c.609-291_609-290delTT	intron	N/A	NP_004324.2
BRAF	NM_001374244.1		c.609-291_609-290delTT	intron	N/A	NP_001361173.1	A0A2U3TZI2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
BRAF	ENST00000644969.2	MANE Plus Clinical	c.609-291_609-290delTT	intron	N/A	ENSP00000496776.1	A0A2R8Y8E0
BRAF	ENST00000646891.2	MANE Select	c.609-291_609-290delTT	intron	N/A	ENSP00000493543.1	P15056
BRAF	ENST00000288602.11	TSL:1	c.609-291_609-290delTT	intron	N/A	ENSP00000288602.7	A0A2U3TZI2

Frequencies

GnomAD3 genomes

AF:

0.0516

AC:

2167

AN:

42026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0246

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00393

Gnomad SAS

AF:

0.0549

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0204

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.0406

GnomAD2 exomes

AF:

0.0963

AC:

2210

AN:

22952

AF XY:

0.0885

show subpopulations

Gnomad AFR exome

AF:

0.141

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.0588

Gnomad EAS exome

AF:

0.133

Gnomad FIN exome

AF:

0.0680

Gnomad NFE exome

AF:

0.0816

Gnomad OTH exome

AF:

0.102

GnomAD4 exome

AF:

0.111

AC:

16654

AN:

150088

Hom.:

AF XY:

0.110

AC XY:

9704

AN XY:

88134

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.127

AC:

367

AN:

2890

American (AMR)

AF:

0.110

AC:

800

AN:

7292

Ashkenazi Jewish (ASJ)

AF:

0.0822

AC:

341

AN:

4150

East Asian (EAS)

AF:

0.102

AC:

492

AN:

4800

South Asian (SAS)

AF:

0.110

AC:

3131

AN:

28462

European-Finnish (FIN)

AF:

0.116

AC:

750

AN:

6490

Middle Eastern (MID)

AF:

0.0956

AC:

AN:

586

European-Non Finnish (NFE)

AF:

0.112

AC:

9937

AN:

88486

Other (OTH)

AF:

0.113

AC:

780

AN:

6932

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.327

Heterozygous variant carriers

1074

2148

3223

4297

5371

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

140

210

280

350

<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:

0.0517

AC:

2172

AN:

42014

Hom.:

Cov.:

AF XY:

0.0517

AC XY:

1017

AN XY:

19676

show subpopulations

African (AFR)

AF:

0.142

AC:

1952

AN:

13760

American (AMR)

AF:

0.0246

AC:

AN:

3254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1250

East Asian (EAS)

AF:

0.00394

AC:

AN:

1268

South Asian (SAS)

AF:

0.0547

AC:

AN:

1354

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1270

Middle Eastern (MID)

AF:

0.0213

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00190

AC:

AN:

18956

Other (OTH)

AF:

0.0421

AC:

AN:

546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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