rs2270238

Positions:

• chr12-10309917-C-T

Variant summary

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

The NM_002262.5(KLRD1):​c.163+229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,024 control chromosomes in the GnomAD database, including 5,183 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 0.24 (5183 hom., cov: 32)
• Consequence: KLRD1 NM_002262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963

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]

KLRD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRD1	NM_002262.5	c.163+229C>T		intron_variant		ENST00000336164.9	NP_002253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000336164.9	c.163+229C>T		intron_variant		1	NM_002262.5	ENSP00000338130.4

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35825 AN: 151906 Hom.: 5179 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.236 AC: 35840 AN: 152024 Hom.: 5183 Cov.: 32 AF XY: 0.242 AC XY: 17984 AN XY: 74294

Gnomad4 AFR AF: 0.0624

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.320

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.339

Gnomad4 NFE AF: 0.296

Gnomad4 OTH AF: 0.235

Alfa AF: 0.286 Hom.: 12760

Bravo AF: 0.228

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.61

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: rs2270238; hg19: chr12-10462516;