rs12829155

Positions:

• chr12-10315655-A-G
• chr12-10315655-A-T

Variant summary

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

The ENST00000336164.9(KLRD1):​c.*862A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,882 control chromosomes in the GnomAD database, including 19,908 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 0.49 (19908 hom., cov: 31)
  • Exomes 𝑓: 0.68 (63 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLRD1 ENST00000336164.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

Genes affected

KLRD1 (HGNC:6378): (killer cell lectin like receptor D1) Natural killer (NK) cells are a distinct lineage of lymphocytes that mediate cytotoxic activity and secrete cytokines upon immune stimulation. Several genes of the C-type lectin superfamily, including members of the NKG2 family, are expressed by NK cells and may be involved in the regulation of NK cell function. KLRD1 (CD94) is an antigen preferentially expressed on NK cells and is classified as a type II membrane protein because it has an external C terminus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRD1	NM_002262.5	c.*862A>G		3_prime_UTR_variant	6/6	ENST00000336164.9	NP_002253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000336164.9	c.*862A>G		3_prime_UTR_variant	6/6	1	NM_002262.5	ENSP00000338130	P1
KLRD1	ENST00000350274.9	c.*862A>G		3_prime_UTR_variant	5/5	1		ENSP00000310929
KLRD1	ENST00000381908.7	c.*862A>G		3_prime_UTR_variant	7/7	1		ENSP00000371333	P1
KLRD1	ENST00000539792.1			downstream_gene_variant		5		ENSP00000437880

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73788 AN: 151764 Hom.: 19910 Cov.: 31

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.743

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.596

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.507

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.680 AC: 193 AN: 284 Hom.: 63 Cov.: 0 AF XY: 0.652 AC XY: 116 AN XY: 178

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.700

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 0.944

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.674

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.486 AC: 73788 AN: 151882 Hom.: 19908 Cov.: 31 AF XY: 0.487 AC XY: 36110 AN XY: 74218

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.492

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.437

Gnomad4 SAS AF: 0.671

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.510

Alfa AF: 0.434 Hom.: 1419

Bravo AF: 0.468

Asia WGS AF: 0.548 AC: 1903 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.3
DANN	Benign	0.49

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: rs12829155; hg19: chr12-10468254;