12-88566950-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+13314G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,088 control chromosomes in the GnomAD database, including 38,565 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 0.67 (38565 hom., cov: 32)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KITLG	NM_000899.5	c.15+13314G>A		intron_variant		ENST00000644744.1
KITLG	NM_003994.6	c.15+13314G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KITLG	ENST00000644744.1	c.15+13314G>A		intron_variant			NM_000899.5	P1

Frequencies

GnomAD3 genomes AF: 0.675 AC: 102521 AN: 151970 Hom.: 38562 Cov.: 32

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.752

Gnomad AMR AF: 0.801

Gnomad ASJ AF: 0.860

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.806

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.817

Gnomad OTH AF: 0.714

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

GnomAD4 genome AF: 0.674 AC: 102543 AN: 152088 Hom.: 38565 Cov.: 32 AF XY: 0.682 AC XY: 50679 AN XY: 74350

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.801

Gnomad4 ASJ AF: 0.860

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.817

Gnomad4 OTH AF: 0.714

Alfa AF: 0.757 Hom.: 9900

Bravo AF: 0.652

Asia WGS AF: 0.729 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.18
Dann	Benign	0.62

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: rs1352947; hg19: chr12-88960727;