rs2046971

Positions:

• chr12-88565733-G-C

Variant summary

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

The NM_000899.5(KITLG):​c.15+14531C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 152,122 control chromosomes in the GnomAD database, including 36,723 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 0.66 (36723 hom., cov: 32)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.795 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KITLG	NM_000899.5	c.15+14531C>G		intron_variant		ENST00000644744.1
KITLG	NM_003994.6	c.15+14531C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KITLG	ENST00000644744.1	c.15+14531C>G		intron_variant			NM_000899.5	P1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100155 AN: 152004 Hom.: 36719 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.783

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.700

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

GnomAD4 genome AF: 0.659 AC: 100179 AN: 152122 Hom.: 36723 Cov.: 32 AF XY: 0.664 AC XY: 49356 AN XY: 74362

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.858

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.783

Gnomad4 NFE AF: 0.800

Gnomad4 OTH AF: 0.701

Alfa AF: 0.720 Hom.: 5247

Bravo AF: 0.640

Asia WGS AF: 0.726 AC: 2524 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.65

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: rs2046971; hg19: chr12-88959510;