12-88561865-C-T

Variant names:

• chr12-88561865-C-T
• rs1907703
• NM_000899.5:c.16-16000G>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.16-16000G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.658 in 152,080 control chromosomes in the GnomAD database, including 36,704 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 (36704 hom., cov: 32)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.691
• Publications: 5 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

LOC124902979 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.16-16000G>A		intron_variant	Intron 1 of 9	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.16-16000G>A		intron_variant	Intron 1 of 8		NP_003985.2
LOC124902979	XR_007063398.1	n.1186-2269G>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.16-16000G>A		intron_variant	Intron 1 of 9		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100104 AN: 151962 Hom.: 36700 Cov.: 32

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.857

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.658 AC: 100128 AN: 152080 Hom.: 36704 Cov.: 32 AF XY: 0.664 AC XY: 49344 AN XY: 74354

African (AFR) AF: 0.302 AC: 12502 AN: 41456

American (AMR) AF: 0.782 AC: 11950 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.857 AC: 2975 AN: 3470

East Asian (EAS) AF: 0.722 AC: 3731 AN: 5170

South Asian (SAS) AF: 0.805 AC: 3887 AN: 4828

European-Finnish (FIN) AF: 0.784 AC: 8285 AN: 10572

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54381 AN: 67986

Other (OTH) AF: 0.700 AC: 1479 AN: 2114

Alfa AF: 0.624 Hom.: 2574

Bravo AF: 0.640

Asia WGS AF: 0.726 AC: 2525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.60
DANN	Benign	0.26
PhyloP100		-0.69
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: rs1907703; hg19: chr12-88955642;