chr7-140808351-CAAAA-C

Variant names:

Variant summary

Our verdict is . The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_004333.6(BRAF):c.609-293_609-290delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 149,804 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. Variant has been reported in ClinVar as Benign (★). The gene BRAF is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 21)

Exomes 𝑓: 0.047 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

BRAF
NM_004333.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.483

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: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 7-140808351-CAAAA-C is Benign according to our data. Variant chr7-140808351-CAAAA-C is described in ClinVar as Benign. ClinVar VariationId is 1239626.Status of the report is criteria_provided_single_submitter, 1 stars.

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.609-293_609-290delTTTT	intron	N/A	NP_001361187.1	A0A2R8Y8E0
BRAF	NM_004333.6	MANE Select	c.609-293_609-290delTTTT	intron	N/A	NP_004324.2
BRAF	NM_001374244.1		c.609-293_609-290delTTTT	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.609-293_609-290delTTTT	intron	N/A	ENSP00000496776.1	A0A2R8Y8E0
BRAF	ENST00000646891.2	MANE Select	c.609-293_609-290delTTTT	intron	N/A	ENSP00000493543.1	P15056
BRAF	ENST00000288602.11	TSL:1	c.609-293_609-290delTTTT	intron	N/A	ENSP00000288602.7	A0A2U3TZI2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

42124

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0401

AC:

920

AN:

22952

AF XY:

0.0376

show subpopulations

Gnomad AFR exome

AF:

0.0635

Gnomad AMR exome

AF:

0.0610

Gnomad ASJ exome

AF:

0.0253

Gnomad EAS exome

AF:

0.0544

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.0312

Gnomad OTH exome

AF:

0.0487

GnomAD4 exome

AF:

0.0466

AC:

6983

AN:

149804

Hom.:

AF XY:

0.0458

AC XY:

4027

AN XY:

88014

show subpopulations

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

African (AFR)

AF:

0.0616

AC:

177

AN:

2874

American (AMR)

AF:

0.0544

AC:

395

AN:

7264

Ashkenazi Jewish (ASJ)

AF:

0.0348

AC:

144

AN:

4138

East Asian (EAS)

AF:

0.0451

AC:

214

AN:

4742

South Asian (SAS)

AF:

0.0462

AC:

1317

AN:

28528

European-Finnish (FIN)

AF:

0.0442

AC:

286

AN:

6464

Middle Eastern (MID)

AF:

0.0599

AC:

AN:

584

European-Non Finnish (NFE)

AF:

0.0463

AC:

4092

AN:

88322

Other (OTH)

AF:

0.0469

AC:

323

AN:

6888

⚠️ 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: 0.296

Heterozygous variant carriers

519

1037

1556

2074

2593

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

128

160

<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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

42124

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

19714

African (AFR)

AF:

0.00

AC:

AN:

13840

American (AMR)

AF:

0.00

AC:

AN:

3258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1250

East Asian (EAS)

AF:

0.00

AC:

AN:

1272

South Asian (SAS)

AF:

0.00

AC:

AN:

1370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1270

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

18962

Other (OTH)

AF:

0.00

AC:

AN:

542

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

0.48

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over