NM_000899.5:c.16-15827C>T

Variant names:

• chr12-88561692-G-A
• rs1907702
• NM_000899.5:c.16-15827C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000899.5(KITLG):​c.16-15827C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,066 control chromosomes in the GnomAD database, including 34,518 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 0.62 (34518 hom., cov: 32)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.16-15827C>T		intron_variant	Intron 1 of 9	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.16-15827C>T		intron_variant	Intron 1 of 8		NP_003985.2
LOC124902979	XR_007063398.1	n.1186-2096C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.16-15827C>T		intron_variant	Intron 1 of 9		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93686 AN: 151948 Hom.: 34514 Cov.: 32

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.855

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.793

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.616 AC: 93692 AN: 152066 Hom.: 34518 Cov.: 32 AF XY: 0.622 AC XY: 46223 AN XY: 74342

African (AFR) AF: 0.178 AC: 7392 AN: 41446

American (AMR) AF: 0.764 AC: 11682 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 2962 AN: 3466

East Asian (EAS) AF: 0.720 AC: 3713 AN: 5156

South Asian (SAS) AF: 0.710 AC: 3416 AN: 4814

European-Finnish (FIN) AF: 0.781 AC: 8267 AN: 10588

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.793 AC: 53920 AN: 67992

Other (OTH) AF: 0.667 AC: 1412 AN: 2116

Alfa AF: 0.734 Hom.: 54364

Bravo AF: 0.594

Asia WGS AF: 0.677 AC: 2353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.17
DANN	Benign	0.54
PhyloP100		-2.3
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: rs1907702; hg19: chr12-88955469;