rs995030

Variant names:

• chr12-88496894-A-G
• rs995030
• ENST00000378535.4:n.1090T>C

Variant summary

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

The ENST00000378535.4(KITLG):​n.1090T>C 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 0.68 in 161,158 control chromosomes in the GnomAD database, including 40,827 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 0.67 (37972 hom., cov: 32)
  • Exomes 𝑓: 0.79 (2855 hom.)
• Consequence: KITLG ENST00000378535.4 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983
• Publications: 78 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KITLG	NM_000899.5	c.*325T>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000644744.1	NP_000890.1
KITLG	NM_003994.6	c.*325T>C		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.*325T>C		3_prime_UTR_variant	Exon 10 of 10		NM_000899.5	ENSP00000495951.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102479 AN: 151978 Hom.: 37966 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.755

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.788

Gnomad MID AF: 0.851

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.709

GnomAD4 exome AF: 0.786 AC: 7123 AN: 9064 Hom.: 2855 Cov.: 0 AF XY: 0.785 AC XY: 3909 AN XY: 4982

African (AFR) AF: 0.266 AC: 33 AN: 124

American (AMR) AF: 0.835 AC: 162 AN: 194

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 177 AN: 208

East Asian (EAS) AF: 0.679 AC: 125 AN: 184

South Asian (SAS) AF: 0.787 AC: 1145 AN: 1454

European-Finnish (FIN) AF: 0.789 AC: 920 AN: 1166

Middle Eastern (MID) AF: 0.833 AC: 40 AN: 48

European-Non Finnish (NFE) AF: 0.797 AC: 4177 AN: 5240

Other (OTH) AF: 0.771 AC: 344 AN: 446

GnomAD4 genome AF: 0.674 AC: 102504 AN: 152094 Hom.: 37972 Cov.: 32 AF XY: 0.679 AC XY: 50475 AN XY: 74364

African (AFR) AF: 0.333 AC: 13809 AN: 41466

American (AMR) AF: 0.790 AC: 12056 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2995 AN: 3472

East Asian (EAS) AF: 0.746 AC: 3865 AN: 5178

South Asian (SAS) AF: 0.807 AC: 3891 AN: 4820

European-Finnish (FIN) AF: 0.788 AC: 8341 AN: 10582

Middle Eastern (MID) AF: 0.853 AC: 249 AN: 292

European-Non Finnish (NFE) AF: 0.810 AC: 55108 AN: 67994

Other (OTH) AF: 0.711 AC: 1503 AN: 2114

Alfa AF: 0.772 Hom.: 186416

Bravo AF: 0.656

Asia WGS AF: 0.739 AC: 2570 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.0
DANN	Benign	0.66
PhyloP100		0.98
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: rs995030; hg19: chr12-88890671; COSMIC: COSV57201343; COSMIC: COSV57201343;