chr12-88573230-C-T

Variant names:

• chr12-88573230-C-T
• rs10506957
• NM_000899.5:c.15+7034G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

KITLG Gene-Disease associations (from GenCC):

• autosomal dominant nonsyndromic hearing loss 69

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
• hyperpigmentation with or without hypopigmentation, familial progressive

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• autosomal dominant nonsyndromic hearing loss

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial progressive hyper- and hypopigmentation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• familial progressive hyperpigmentation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Waardenburg syndrome type 2

  Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• Waardenburg syndrome, IIa 2F

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.15+7034G>A		intron_variant	Intron 1 of 9	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.15+7034G>A		intron_variant	Intron 1 of 8		NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.15+7034G>A		intron_variant	Intron 1 of 9		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

African (AFR) AF: 0.182 AC: 7543 AN: 41430

American (AMR) AF: 0.783 AC: 11963 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.856 AC: 2970 AN: 3468

East Asian (EAS) AF: 0.721 AC: 3720 AN: 5158

South Asian (SAS) AF: 0.711 AC: 3428 AN: 4818

European-Finnish (FIN) AF: 0.850 AC: 8993 AN: 10586

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55055 AN: 67970

Other (OTH) AF: 0.684 AC: 1441 AN: 2106

Alfa AF: 0.779 Hom.: 24850

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
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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