GeneBe

NM_001374258.1:c.2248-10_2248-5delTTTTTT

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001374258.1(BRAF):​c.2248-10_2248-5delTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 27)
Exomes 𝑓: 0.0000013 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BRAF
NM_001374258.1 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.67

Publications

3 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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRAFNM_001374258.1 linkc.2248-10_2248-5delTTTTTT splice_region_variant, intron_variant Intron 18 of 19 ENST00000644969.2 NP_001361187.1
BRAFNM_004333.6 linkc.2128-10_2128-5delTTTTTT splice_region_variant, intron_variant Intron 17 of 17 ENST00000646891.2 NP_004324.2 P15056

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRAFENST00000644969.2 linkc.2248-10_2248-5delTTTTTT splice_region_variant, intron_variant Intron 18 of 19 NM_001374258.1 ENSP00000496776.1 A0A2R8Y8E0
BRAFENST00000646891.2 linkc.2128-10_2128-5delTTTTTT splice_region_variant, intron_variant Intron 17 of 17 NM_004333.6 ENSP00000493543.1 P15056

Frequencies

GnomAD3 genomes
Cov.:
27
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000133
AC:
1
AN:
749278
Hom.:
0
AF XY:
0.00000265
AC XY:
1
AN XY:
377318
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
16176
American (AMR)
AF:
0.00
AC:
0
AN:
15314
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12782
East Asian (EAS)
AF:
0.00
AC:
0
AN:
22256
South Asian (SAS)
AF:
0.00
AC:
0
AN:
36136
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
23692
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2692
European-Non Finnish (NFE)
AF:
0.00000170
AC:
1
AN:
589320
Other (OTH)
AF:
0.00
AC:
0
AN:
30910
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.775
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
27
Alfa
AF:
0.00
Hom.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.7

Splicing

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

Publications

Other links and lift over

dbSNP: rs373442098; hg19: chr7-140434574; API