rs995029

Variant names:

• chr12-88496744-C-T
• rs995029
• ENST00000378535.4:n.1240G>A

Variant summary

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

The ENST00000378535.4(KITLG):​n.1240G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 153,160 control chromosomes in the GnomAD database, including 49,206 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 0.78 (48760 hom., cov: 32)
  • Exomes 𝑓: 0.89 (446 hom.)
• Consequence: KITLG ENST00000378535.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.394
• Publications: 12 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.*475G>A		3_prime_UTR_variant	Exon 10 of 10	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.*475G>A		3_prime_UTR_variant	Exon 9 of 9		NP_003985.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KITLG	ENST00000644744.1	c.*475G>A		3_prime_UTR_variant	Exon 10 of 10		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.776 AC: 117929 AN: 151918 Hom.: 48747 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.871

Gnomad ASJ AF: 0.926

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.895

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.915

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.817

GnomAD4 exome AF: 0.892 AC: 1003 AN: 1124 Hom.: 446 Cov.: 0 AF XY: 0.899 AC XY: 543 AN XY: 604

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.917 AC: 33 AN: 36

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 10 AN: 12

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.850 AC: 51 AN: 60

European-Finnish (FIN) AF: 0.873 AC: 398 AN: 456

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.913 AC: 482 AN: 528

Other (OTH) AF: 0.962 AC: 25 AN: 26

GnomAD4 genome AF: 0.776 AC: 117967 AN: 152036 Hom.: 48760 Cov.: 32 AF XY: 0.778 AC XY: 57811 AN XY: 74330

African (AFR) AF: 0.463 AC: 19167 AN: 41436

American (AMR) AF: 0.870 AC: 13275 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.926 AC: 3213 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3916 AN: 5148

South Asian (SAS) AF: 0.896 AC: 4323 AN: 4824

European-Finnish (FIN) AF: 0.869 AC: 9203 AN: 10592

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62119 AN: 67996

Other (OTH) AF: 0.817 AC: 1727 AN: 2114

Alfa AF: 0.819 Hom.: 15138

Bravo AF: 0.758

Asia WGS AF: 0.797 AC: 2774 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.4
DANN	Benign	0.47
PhyloP100		0.39
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: rs995029; hg19: chr12-88890521; COSMIC: COSV57200475; COSMIC: COSV57200475;