chr12-88559784-C-A

Variant names:

• chr12-88559784-C-A
• rs3782181
• NM_000899.5:c.16-13919G>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.16-13919G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,052 control chromosomes in the GnomAD database, including 36,450 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 (36450 hom., cov: 32)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.311
• Publications: 37 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.793 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.16-13919G>T		intron_variant	Intron 1 of 9	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.16-13919G>T		intron_variant	Intron 1 of 8		NP_003985.2
LOC124902979	XR_007063398.1	n.1186-188G>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.16-13919G>T		intron_variant	Intron 1 of 9		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99585 AN: 151934 Hom.: 36446 Cov.: 32

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.856

Gnomad EAS AF: 0.722

Gnomad SAS AF: 0.795

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.655 AC: 99607 AN: 152052 Hom.: 36450 Cov.: 32 AF XY: 0.660 AC XY: 49055 AN XY: 74298

African (AFR) AF: 0.294 AC: 12191 AN: 41438

American (AMR) AF: 0.780 AC: 11920 AN: 15290

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

East Asian (EAS) AF: 0.722 AC: 3725 AN: 5158

South Asian (SAS) AF: 0.797 AC: 3842 AN: 4820

European-Finnish (FIN) AF: 0.782 AC: 8266 AN: 10566

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54287 AN: 67998

Other (OTH) AF: 0.697 AC: 1471 AN: 2110

Alfa AF: 0.758 Hom.: 167217

Bravo AF: 0.636

Asia WGS AF: 0.721 AC: 2507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.82
DANN	Benign	0.51
PhyloP100		-0.31
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: rs3782181; hg19: chr12-88953561;