chr12-88573230-C-T

Position:

• chr12-88573230-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.15+7034G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.632 in 152,018 control chromosomes in the GnomAD database, including 36,309 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 0.63 (36309 hom., cov: 31)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KITLG	NM_000899.5	c.15+7034G>A		intron_variant		ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.15+7034G>A		intron_variant			NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.15+7034G>A		intron_variant			NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.632 AC: 96037 AN: 151900 Hom.: 36305 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.783

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.721

Gnomad SAS AF: 0.710

Gnomad FIN AF: 0.850

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.632 AC: 96042 AN: 152018 Hom.: 36309 Cov.: 31 AF XY: 0.640 AC XY: 47543 AN XY: 74316

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.783

Gnomad4 ASJ AF: 0.856

Gnomad4 EAS AF: 0.721

Gnomad4 SAS AF: 0.711

Gnomad4 FIN AF: 0.850

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.684

Alfa AF: 0.768 Hom.: 14712

Bravo AF: 0.606

Asia WGS AF: 0.679 AC: 2362 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.5
DANN	Benign	0.66

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: rs10506957; hg19: chr12-88967007; COSMIC: COSV57203350;