rs995029

Positions:

• chr12-88496744-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000899.5(KITLG):​c.*475G>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 0.777 in 153,160 control chromosomes in the GnomAD database, including 49,206 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 0.78 (48760 hom., cov: 32)
  • Exomes 𝑓: 0.89 (446 hom.)
• Consequence: KITLG NM_000899.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394

Genes affected

KITLG (HGNC:6343): (KIT ligand) This gene encodes the ligand of the tyrosine-kinase receptor encoded by the KIT locus. This ligand is a pleiotropic factor that acts in utero in germ cell and neural cell development, and hematopoiesis, all believed to reflect a role in cell migration. In adults, it functions pleiotropically, while mostly noted for its continued requirement in hematopoiesis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KITLG	NM_000899.5	c.*475G>A		3_prime_UTR_variant	10/10	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.*475G>A		3_prime_UTR_variant	9/9		NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744	c.*475G>A		3_prime_UTR_variant	10/10		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117929 AN: 151918 Hom.: 48747 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.892 AC: 1003 AN: 1124 Hom.: 446 Cov.: 0 AF XY: 0.899 AC XY: 543 AN XY: 604

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.917

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.850

Gnomad4 FIN exome AF: 0.873

Gnomad4 NFE exome AF: 0.913

Gnomad4 OTH exome AF: 0.962

GnomAD4 genome AF: 0.776 AC: 117967 AN: 152036 Hom.: 48760 Cov.: 32 AF XY: 0.778 AC XY: 57811 AN XY: 74330

Gnomad4 AFR AF: 0.463

Gnomad4 AMR AF: 0.870

Gnomad4 ASJ AF: 0.926

Gnomad4 EAS AF: 0.761

Gnomad4 SAS AF: 0.896

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.914

Gnomad4 OTH AF: 0.817

Alfa AF: 0.825 Hom.: 15047

Bravo AF: 0.758

Asia WGS AF: 0.797 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs995029; hg19: chr12-88890521; COSMIC: COSV57200475; COSMIC: COSV57200475;