NM_004333.6(BRAF):c.-19C>T AND not specified

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Nov 25, 2019
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000077864.29

Allele description [Variation Report for NM_004333.6(BRAF):c.-19C>T]

NM_004333.6(BRAF):c.-19C>T

Gene:

BRAF:B-Raf proto-oncogene, serine/threonine kinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q34

Genomic location:

Preferred name:

NM_004333.6(BRAF):c.-19C>T

HGVS:

NC_000007.14:g.140924722G>A
NG_007873.3:g.5043C>T
NM_001354609.2:c.-19C>T
NM_001374244.1:c.-19C>T
NM_001374258.1:c.-19C>T
NM_001378467.1:c.-19C>T
NM_001378468.1:c.-19C>T
NM_001378469.1:c.-19C>T
NM_001378470.1:c.-19C>T
NM_001378471.1:c.-19C>T
NM_001378474.1:c.-19C>T
NM_001378475.1:c.-19C>T
NM_004333.6:c.-19C>TMANE SELECT
LRG_299t1:c.-19C>T
LRG_299:g.5043C>T
NC_000007.13:g.140624522G>A
NM_004333.4:c.-19C>T

Links:

dbSNP: rs71645935

NCBI 1000 Genomes Browser:

rs71645935

Molecular consequence:

NM_001354609.2:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374244.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001374258.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001378467.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001378468.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001378469.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001378470.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001378471.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001378474.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001378475.1:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_004333.6:c.-19C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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PF3D7_1030100 [Plasmodium falciparum 3D7]
PF3D7_1030100 [Plasmodium falciparum 3D7]
Gene ID:810451

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000058304	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Mar 18, 2013)	germline	clinical testing	Citation Link,
SCV000197183	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Jun 1, 2011)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000207625	Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	no assertion criteria provided	Benign (Jan 15, 2015)	germline	clinical testing
SCV000310103	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001363012	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Nov 25, 2019)	germline	clinical testing	Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	4	4	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	5	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Eurofins Ntd Llc (ga), SCV000058304.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	5	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		5	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000197183.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (1)

Description

-19C>T in the 5'UTR of BRAF: This variant has been reported in dbSNP in 2.3% (1/ 44) Hispanic chromosomes and 4.2% (1/24) Black chromosomes (rs71645935). This va riant is located in the 5'UTR and variants in regulatory regions could have an e ffect on transcriptional or translational efficiency. However, no variants in th is region of BRAF have been found to be pathogenic in individuals with Noonan sp ectrum disorders.Therefore, this variant is not expected to have clinical signif icance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		4	not provided	4	not provided

From Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center, SCV000207625.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000310103.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363012.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Variant summary: BRAF c.-19C>T is located in the untranslated mRNA region upstream of the initiation codon. The variant allele was found at a frequency of 0.0011 in 86066 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 455-folds over the estimated maximal expected allele frequency for a pathogenic variant in BRAF causing Noonan Syndrome and Related Conditions phenotype (2.5e-06), strongly suggesting that the variant is benign. Two ClinVar submissions (evaluation after 2014) cites the variant once as likely benign and once as benign. Based on the evidence outlined above, the variant was classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 1, 2024

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