rs17084733

Variant names:

• chr4-54738774-G-A
• rs17084733
• NM_000222.3:c.*217G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-54738774-G-A
• chr4-54738774-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000222.3(KIT):​c.*217G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 632,120 control chromosomes in the GnomAD database, including 3,108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (860 hom., cov: 32)
  • Exomes 𝑓: 0.091 (2248 hom.)
• Consequence: KIT NM_000222.3 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.752
• Publications: 23 publications found

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 Gene-Disease associations (from GenCC):

• gastrointestinal stromal tumor

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics
• piebaldism

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
• cutaneous mastocytosis

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• mastocytosis

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 4-54738774-G-A is Benign according to our data. Variant chr4-54738774-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 348959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIT	NM_000222.3	c.*217G>A		3_prime_UTR_variant	Exon 21 of 21	ENST00000288135.6	NP_000213.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIT	ENST00000288135.6	c.*217G>A		3_prime_UTR_variant	Exon 21 of 21	1	NM_000222.3	ENSP00000288135.6

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15317 AN: 152048 Hom.: 859 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0758

Gnomad ASJ AF: 0.0925

Gnomad EAS AF: 0.0495

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.0361

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0986

Gnomad OTH AF: 0.0956

GnomAD4 exome AF: 0.0906 AC: 43500 AN: 479954 Hom.: 2248 Cov.: 5 AF XY: 0.0912 AC XY: 23172 AN XY: 254056

African (AFR) AF: 0.140 AC: 1894 AN: 13484

American (AMR) AF: 0.0581 AC: 1407 AN: 24200

Ashkenazi Jewish (ASJ) AF: 0.0975 AC: 1456 AN: 14928

East Asian (EAS) AF: 0.0490 AC: 1554 AN: 31688

South Asian (SAS) AF: 0.0947 AC: 4646 AN: 49062

European-Finnish (FIN) AF: 0.0484 AC: 1483 AN: 30634

Middle Eastern (MID) AF: 0.0857 AC: 176 AN: 2054

European-Non Finnish (NFE) AF: 0.0983 AC: 28166 AN: 286642

Other (OTH) AF: 0.0997 AC: 2718 AN: 27262

GnomAD4 genome AF: 0.101 AC: 15323 AN: 152166 Hom.: 860 Cov.: 32 AF XY: 0.0951 AC XY: 7077 AN XY: 74400

African (AFR) AF: 0.140 AC: 5793 AN: 41514

American (AMR) AF: 0.0757 AC: 1156 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0925 AC: 321 AN: 3470

East Asian (EAS) AF: 0.0496 AC: 257 AN: 5178

South Asian (SAS) AF: 0.0952 AC: 458 AN: 4812

European-Finnish (FIN) AF: 0.0361 AC: 383 AN: 10596

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0985 AC: 6700 AN: 67996

Other (OTH) AF: 0.0974 AC: 206 AN: 2114

Alfa AF: 0.0992 Hom.: 995

Bravo AF: 0.106

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30983504, 21119596, 16365291) -

Gastrointestinal stromal tumor Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.6
DANN	Benign	0.60
PhyloP100		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17084733; hg19: chr4-55604940;