GeneBe

7-140924708-T-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001374258.1(BRAF):​c.-5A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000121 in 825,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000012 ( 0 hom. )

Consequence

BRAF
NM_001374258.1 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

0 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), 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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.44).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRAFNM_001374258.1 linkc.-5A>C 5_prime_UTR_variant Exon 1 of 20 ENST00000644969.2 NP_001361187.1
BRAFNM_004333.6 linkc.-5A>C 5_prime_UTR_variant Exon 1 of 18 ENST00000646891.2 NP_004324.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRAFENST00000644969.2 linkc.-5A>C 5_prime_UTR_variant Exon 1 of 20 NM_001374258.1 ENSP00000496776.1
BRAFENST00000646891.2 linkc.-5A>C 5_prime_UTR_variant Exon 1 of 18 NM_004333.6 ENSP00000493543.1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000121
AC:
1
AN:
825994
Hom.:
0
Cov.:
11
AF XY:
0.00
AC XY:
0
AN XY:
427612
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
17118
American (AMR)
AF:
0.00
AC:
0
AN:
31680
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
20672
East Asian (EAS)
AF:
0.00
AC:
0
AN:
29286
South Asian (SAS)
AF:
0.00
AC:
0
AN:
65894
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
32978
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2956
European-Non Finnish (NFE)
AF:
0.00000171
AC:
1
AN:
586412
Other (OTH)
AF:
0.00
AC:
0
AN:
38998
⚠️ 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: 0.275
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
CADD
Benign
17
DANN
Benign
0.78
PhyloP100
1.1
PromoterAI
0.40
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3

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

Other links and lift over

dbSNP: rs71645936; hg19: chr7-140624508; API