rs2017472

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000288135.6(KIT):​c.67+12767T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,992 control chromosomes in the GnomAD database, including 18,336 homozygotes. 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: 𝑓 0.48 ( 18336 hom., cov: 32)

Consequence

KIT
ENST00000288135.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.54
Variant links:
Genes affected
KIT (HGNC:6342): (KIT proto-oncogene, receptor tyrosine kinase) This gene encodes a receptor tyrosine kinase. This gene was initially identified as a homolog of the feline sarcoma viral oncogene v-kit and is often referred to as proto-oncogene c-Kit. The canonical form of this glycosylated transmembrane protein has an N-terminal extracellular region with five immunoglobulin-like domains, a transmembrane region, and an intracellular tyrosine kinase domain at the C-terminus. Upon activation by its cytokine ligand, stem cell factor (SCF), this protein phosphorylates multiple intracellular proteins that play a role in in the proliferation, differentiation, migration and apoptosis of many cell types and thereby plays an important role in hematopoiesis, stem cell maintenance, gametogenesis, melanogenesis, and in mast cell development, migration and function. This protein can be a membrane-bound or soluble protein. Mutations in this gene are associated with gastrointestinal stromal tumors, mast cell disease, acute myelogenous leukemia, and piebaldism. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2020]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.02).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
KITNM_000222.3 linkuse as main transcriptc.67+12767T>C intron_variant ENST00000288135.6 NP_000213.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
KITENST00000288135.6 linkuse as main transcriptc.67+12767T>C intron_variant 1 NM_000222.3 ENSP00000288135 P4P10721-1

Frequencies

GnomAD3 genomes
AF:
0.485
AC:
73614
AN:
151872
Hom.:
18313
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.583
Gnomad AMI
AF:
0.482
Gnomad AMR
AF:
0.504
Gnomad ASJ
AF:
0.397
Gnomad EAS
AF:
0.208
Gnomad SAS
AF:
0.313
Gnomad FIN
AF:
0.496
Gnomad MID
AF:
0.361
Gnomad NFE
AF:
0.458
Gnomad OTH
AF:
0.453
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.485
AC:
73680
AN:
151992
Hom.:
18336
Cov.:
32
AF XY:
0.482
AC XY:
35786
AN XY:
74298
show subpopulations
Gnomad4 AFR
AF:
0.583
Gnomad4 AMR
AF:
0.503
Gnomad4 ASJ
AF:
0.397
Gnomad4 EAS
AF:
0.207
Gnomad4 SAS
AF:
0.313
Gnomad4 FIN
AF:
0.496
Gnomad4 NFE
AF:
0.458
Gnomad4 OTH
AF:
0.452
Alfa
AF:
0.481
Hom.:
2809
Bravo
AF:
0.494
Asia WGS
AF:
0.294
AC:
1023
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-1.0
CADD
Benign
0.27
DANN
Benign
0.27

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2017472; hg19: chr4-55537014; API