12-88562848-T-C

Variant names:

• chr12-88562848-T-C
• rs1798011
• NM_000899.5:c.16-16983A>G

Variant summary

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

The NM_000899.5(KITLG):​c.16-16983A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.936 in 152,240 control chromosomes in the GnomAD database, including 66,746 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 0.94 (66746 hom., cov: 31)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.16-16983A>G		intron_variant	Intron 1 of 9	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.16-16983A>G		intron_variant	Intron 1 of 8		NP_003985.2
LOC124902979	XR_007063398.1	n.1185+1360A>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.16-16983A>G		intron_variant	Intron 1 of 9		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142391 AN: 152122 Hom.: 66697 Cov.: 31

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.936 AC: 142497 AN: 152240 Hom.: 66746 Cov.: 31 AF XY: 0.935 AC XY: 69596 AN XY: 74422

African (AFR) AF: 0.965 AC: 40079 AN: 41542

American (AMR) AF: 0.939 AC: 14365 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3253 AN: 3472

East Asian (EAS) AF: 0.981 AC: 5069 AN: 5168

South Asian (SAS) AF: 0.961 AC: 4637 AN: 4826

European-Finnish (FIN) AF: 0.893 AC: 9458 AN: 10588

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.921 AC: 62648 AN: 68026

Other (OTH) AF: 0.927 AC: 1957 AN: 2112

Alfa AF: 0.935 Hom.: 11328

Bravo AF: 0.938

Asia WGS AF: 0.969 AC: 3369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.27
PhyloP100		-0.45
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: rs1798011; hg19: chr12-88956625;