rs995030

Positions:

• chr12-88496894-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000899.5(KITLG):​c.*325T>C variant causes a 3 prime UTR 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 NM_000899.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.983

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
KITLG	NM_000899.5	c.*325T>C		3_prime_UTR_variant	10/10	ENST00000644744.1
KITLG	NM_003994.6	c.*325T>C		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KITLG	ENST00000644744.1	c.*325T>C		3_prime_UTR_variant	10/10		NM_000899.5	P1
KITLG	ENST00000347404.10	c.*325T>C		3_prime_UTR_variant	9/9	1
KITLG	ENST00000378535.4	n.1090T>C		non_coding_transcript_exon_variant	9/9	1
KITLG	ENST00000646633.1	c.*1148T>C		3_prime_UTR_variant, NMD_transcript_variant	10/10

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

Gnomad4 AFR exome AF: 0.266

Gnomad4 AMR exome AF: 0.835

Gnomad4 ASJ exome AF: 0.851

Gnomad4 EAS exome AF: 0.679

Gnomad4 SAS exome AF: 0.787

Gnomad4 FIN exome AF: 0.789

Gnomad4 NFE exome AF: 0.797

Gnomad4 OTH exome AF: 0.771

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

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.790

Gnomad4 ASJ AF: 0.863

Gnomad4 EAS AF: 0.746

Gnomad4 SAS AF: 0.807

Gnomad4 FIN AF: 0.788

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.711

Alfa AF: 0.791 Hom.: 83247

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs995030; hg19: chr12-88890671; COSMIC: COSV57201343; COSMIC: COSV57201343;