rs370130654

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_001374258.1(BRAF):c.1323C>T(p.Thr441Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T441T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000056 ( 0 hom. )

Consequence

BRAF
NM_001374258.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.66

Publications

2 publications found

Variant links:

COSMIC-nc: COSV56266824

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:

ENSG00000289788 (HGNC:):

ENSG00000289788 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.084).

BP6

Variant 7-140783132-G-A is Benign according to our data. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-140783132-G-A is described in CliVar as Likely_benign. Clinvar id is 44796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.66 with no splicing effect.

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRAF	NM_001374258.1 link	c.1323C>T	p.Thr441Thr	synonymous_variant	Exon 11 of 20	ENST00000644969.2	NP_001361187.1
BRAF	NM_004333.6 link	c.1203C>T	p.Thr401Thr	synonymous_variant	Exon 10 of 18	ENST00000646891.2	NP_004324.2	P15056

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRAF	ENST00000644969.2 link	c.1323C>T	p.Thr441Thr	synonymous_variant	Exon 11 of 20		NM_001374258.1	ENSP00000496776.1		A0A2R8Y8E0
BRAF	ENST00000646891.2 link	c.1203C>T	p.Thr401Thr	synonymous_variant	Exon 10 of 18		NM_004333.6	ENSP00000493543.1		P15056

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

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:

0.0000882

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251352

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000561

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

727194

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39678

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000665

AC:

AN:

1111962

Other (OTH)

AF:

0.000116

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152092

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41394

American (AMR)

AF:

0.00

AC:

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

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:

0.0000194

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Nov 25, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is not expected to have clinical significance because it does not a lter an amino acid residue and is not located within the splice consensus sequen ce. -

Feb 28, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

May 30, 2022

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Noonan syndrome and Noonan-related syndrome

Benign:1

Mar 23, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

RASopathy

Benign:1

Nov 11, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.69

CADD

Benign

2.9

(source)

DANN

Benign

0.62

PhyloP100

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over