rs11104947

Positions:

• chr12-88549203-G-A

Variant summary

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

The NM_000899.5(KITLG):​c.16-3338C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 152,230 control chromosomes in the GnomAD database, including 62 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 0.014 (62 hom., cov: 32)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KITLG	NM_000899.5	c.16-3338C>T		intron_variant		ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.16-3338C>T		intron_variant			NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.16-3338C>T		intron_variant			NM_000899.5	ENSP00000495951	P1

Frequencies

GnomAD3 genomes AF: 0.0136 AC: 2075 AN: 152112 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.00249

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00943

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.00685

Gnomad FIN AF: 0.0263

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0129

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

GnomAD4 genome AF: 0.0136 AC: 2072 AN: 152230 Hom.: 62 Cov.: 32 AF XY: 0.0143 AC XY: 1063 AN XY: 74422

Gnomad4 AFR AF: 0.00248

Gnomad4 AMR AF: 0.00942

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.00664

Gnomad4 FIN AF: 0.0263

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0118 Hom.: 4

Bravo AF: 0.0118

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.4
DANN	Benign	0.60

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: rs11104947; hg19: chr12-88942980;