12-88566950-C-T

Variant names:

• chr12-88566950-C-T
• rs1352947
• NM_000899.5:c.15+13314G>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+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
• 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 Submitted by: Labcorp Genetics (formerly Invitae)
• 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: Orphanet, G2P
• nonsyndromic genetic hearing loss

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

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

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000899.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	NM_000899.5	MANE Select	c.15+13314G>A		intron	N/A	NP_000890.1	P21583-1
	KITLG	NM_003994.6		c.15+13314G>A		intron	N/A	NP_003985.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	ENST00000644744.1	MANE Select	c.15+13314G>A		intron	N/A	ENSP00000495951.1	P21583-1
	KITLG	ENST00000347404.10	TSL:1	c.15+13314G>A		intron	N/A	ENSP00000054216.5	P21583-2
	KITLG	ENST00000874530.1		c.15+13314G>A		intron	N/A	ENSP00000544589.1

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

African (AFR) AF: 0.306 AC: 12660 AN: 41434

American (AMR) AF: 0.801 AC: 12234 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.860 AC: 2985 AN: 3472

East Asian (EAS) AF: 0.722 AC: 3728 AN: 5162

South Asian (SAS) AF: 0.808 AC: 3900 AN: 4826

European-Finnish (FIN) AF: 0.852 AC: 9027 AN: 10598

Middle Eastern (MID) AF: 0.867 AC: 255 AN: 294

European-Non Finnish (NFE) AF: 0.817 AC: 55558 AN: 67998

Other (OTH) AF: 0.714 AC: 1510 AN: 2114

Alfa AF: 0.761 Hom.: 10556

Bravo AF: 0.652

Asia WGS AF: 0.729 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.62
PhyloP100		-1.2
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: rs1352947; hg19: chr12-88960727;