Variant rs17084713 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000222.3(KIT):c.2142-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00469 in 1,460,574 control chromosomes in the GnomAD database, including 250 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 134 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 116 hom. )

Consequence

KIT
NM_000222.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.318

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]

KIT links:

KIT (HGNC:):

KIT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 4-54731292-A-G is Benign according to our data. Variant chr4-54731292-A-G is described in ClinVar as [Benign]. Clinvar id is 255570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KIT	NM_000222.3 linkuse as main transcript	c.2142-36A>G		intron_variant		ENST00000288135.6	NP_000213.1	P10721-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KIT	ENST00000288135.6 linkuse as main transcript	c.2142-36A>G		intron_variant		1	NM_000222.3	ENSP00000288135.6		P10721-1

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3525

AN:

152090

Hom.:

134

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.0187

GnomAD3 exomes

AF:

0.00635

AC:

1590

AN:

250380

Hom.:

AF XY:

0.00454

AC XY:

615

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.0796

Gnomad AMR exome

AF:

0.00625

Gnomad ASJ exome

AF:

0.00249

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000362

Gnomad OTH exome

AF:

0.00329

GnomAD4 exome

AF:

0.00254

AC:

3326

AN:

1308366

Hom.:

116

Cov.:

AF XY:

0.00221

AC XY:

1458

AN XY:

659260

show subpopulations

Gnomad4 AFR exome

AF:

0.0815

Gnomad4 AMR exome

AF:

0.00632

Gnomad4 ASJ exome

AF:

0.00215

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000192

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000155

Gnomad4 OTH exome

AF:

0.00587

GnomAD4 genome

AF:

0.0231

AC:

3523

AN:

152208

Hom.:

134

Cov.:

AF XY:

0.0229

AC XY:

1705

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.0786

Gnomad4 AMR

AF:

0.0125

Gnomad4 ASJ

AF:

0.00230

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.0185

Alfa

AF:

0.00677

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Gastrointestinal stromal tumor

Benign:1

Benign, criteria provided, single submitter

clinical testing

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Jul 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.26

DANN

Benign

0.70

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over