rs3809214

Positions:

• chr12-10306970-G-A
• chr12-10306970-G-C

Variant summary

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

The ENST00000381908.7(KLRD1):​c.-100-1008G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,936 control chromosomes in the GnomAD database, including 24,641 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 0.56 (24641 hom., cov: 32)
• Consequence: KLRD1 ENST00000381908.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRD1	NM_001114396.3	c.-100-1008G>A		intron_variant			NP_001107868.2
KLRD1	NM_001351060.2	c.-100-1008G>A		intron_variant			NP_001337989.1
KLRD1	NM_001351062.2	c.-101+738G>A		intron_variant			NP_001337991.1
KLRD1	XM_047428821.1	c.-101+738G>A		intron_variant			XP_047284777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000381908.7	c.-100-1008G>A		intron_variant		1		ENSP00000371333	P1
KLRD1	ENST00000540271.1	n.251-1008G>A		intron_variant, non_coding_transcript_variant		1
KLRD1	ENST00000544747.5	c.-100-1008G>A		intron_variant		3		ENSP00000438669

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84942 AN: 151818 Hom.: 24636 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.756

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.672

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.594

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

GnomAD4 genome AF: 0.559 AC: 84970 AN: 151936 Hom.: 24641 Cov.: 32 AF XY: 0.558 AC XY: 41413 AN XY: 74240

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.672

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.668

Gnomad4 FIN AF: 0.586

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.598

Alfa AF: 0.627 Hom.: 50550

Bravo AF: 0.550

Asia WGS AF: 0.558 AC: 1938 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.19
DANN	Benign	0.59

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: rs3809214; hg19: chr12-10459569;