12-10265325-C-T

Variant names:

• chr12-10265325-C-T
• rs10845098
• ENST00000540271.1:n.168+39092C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000540271.1(KLRD1):​n.168+39092C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,160 control chromosomes in the GnomAD database, including 53,621 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 0.80 (53621 hom., cov: 32)
• Consequence: KLRD1 ENST00000540271.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.94
• Publications: 0 publications found

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]

ENSG00000309652 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRD1	NM_001351060.2	c.-101+24585C>T		intron_variant	Intron 2 of 8		NP_001337989.1
LOC124902875	XM_047429945.1	c.263-2625G>A		intron_variant	Intron 3 of 4		XP_047285901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000540271.1	n.168+39092C>T		intron_variant	Intron 1 of 5	1
KLRD1	ENST00000544747.5	c.-101+39092C>T		intron_variant	Intron 1 of 5	3		ENSP00000438669.1
ENSG00000309652	ENST00000842798.1	n.128-2625G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122156 AN: 152042 Hom.: 53620 Cov.: 32

Gnomad AFR AF: 0.413

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.942

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.803 AC: 122178 AN: 152160 Hom.: 53621 Cov.: 32 AF XY: 0.808 AC XY: 60117 AN XY: 74398

African (AFR) AF: 0.413 AC: 17094 AN: 41434

American (AMR) AF: 0.908 AC: 13880 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.942 AC: 3269 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4064 AN: 5178

South Asian (SAS) AF: 0.856 AC: 4130 AN: 4824

European-Finnish (FIN) AF: 0.980 AC: 10406 AN: 10616

Middle Eastern (MID) AF: 0.939 AC: 276 AN: 294

European-Non Finnish (NFE) AF: 0.976 AC: 66393 AN: 68026

Other (OTH) AF: 0.833 AC: 1762 AN: 2114

Alfa AF: 0.839 Hom.: 3324

Bravo AF: 0.781

Asia WGS AF: 0.788 AC: 2736 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-2.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10845098; hg19: chr12-10417924;