12-88554201-T-C

Variant names:

• chr12-88554201-T-C
• rs1492354
• NM_000899.5:c.16-8336A>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.16-8336A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,208 control chromosomes in the GnomAD database, including 63,391 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 0.91 (63391 hom., cov: 31)
• Consequence: KITLG NM_000899.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712
• Publications: 3 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 Submitted by: Labcorp Genetics (formerly Invitae)
• 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: Orphanet, G2P
• nonsyndromic genetic hearing loss

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• Waardenburg syndrome, IIa 2F

  Inheritance: AR, Unknown Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000899.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	NM_000899.5	MANE Select	c.16-8336A>G		intron	N/A	NP_000890.1	P21583-1
	KITLG	NM_003994.6		c.16-8336A>G		intron	N/A	NP_003985.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KITLG	ENST00000644744.1	MANE Select	c.16-8336A>G		intron	N/A	ENSP00000495951.1	P21583-1
	KITLG	ENST00000347404.10	TSL:1	c.16-8336A>G		intron	N/A	ENSP00000054216.5	P21583-2
	KITLG	ENST00000874530.1		c.16-8336A>G		intron	N/A	ENSP00000544589.1

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138748 AN: 152090 Hom.: 63349 Cov.: 31

Gnomad AFR AF: 0.882

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.929

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.961

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.915

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

GnomAD4 genome AF: 0.912 AC: 138848 AN: 152208 Hom.: 63391 Cov.: 31 AF XY: 0.912 AC XY: 67844 AN XY: 74406

African (AFR) AF: 0.882 AC: 36616 AN: 41518

American (AMR) AF: 0.929 AC: 14202 AN: 15288

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

East Asian (EAS) AF: 0.980 AC: 5060 AN: 5162

South Asian (SAS) AF: 0.960 AC: 4631 AN: 4822

European-Finnish (FIN) AF: 0.893 AC: 9481 AN: 10614

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

European-Non Finnish (NFE) AF: 0.921 AC: 62646 AN: 68010

Other (OTH) AF: 0.911 AC: 1928 AN: 2116

Alfa AF: 0.918 Hom.: 13107

Bravo AF: 0.911

Asia WGS AF: 0.964 AC: 3352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	10
DANN	Benign	0.81
PhyloP100		0.71
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: rs1492354; hg19: chr12-88947978;