rs10734824

Variant names:

• chr12-10262224-A-G
• rs10734824
• ENST00000540271.1:n.168+35991A>G

Variant summary

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

The ENST00000540271.1(KLRD1):​n.168+35991A>G 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 151,790 control chromosomes in the GnomAD database, including 53,485 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 (53485 hom., cov: 32)
• Consequence: KLRD1 ENST00000540271.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323
• Publications: 1 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=-0.97).
• 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
LOC124902875	XM_047429945.1	c.*86T>C		3_prime_UTR_variant	Exon 5 of 5		XP_047285901.1
KLRD1	NM_001351060.2	c.-101+21484A>G		intron_variant	Intron 2 of 8		NP_001337989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000540271.1	n.168+35991A>G		intron_variant	Intron 1 of 5	1
ENSG00000309652	ENST00000842798.1	n.317T>C		non_coding_transcript_exon_variant	Exon 3 of 3
KLRD1	ENST00000544747.5	c.-101+35991A>G		intron_variant	Intron 1 of 5	3		ENSP00000438669.1

Frequencies

GnomAD3 genomes AF: 0.804 AC: 121887 AN: 151674 Hom.: 53485 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.784

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: 121907 AN: 151790 Hom.: 53485 Cov.: 32 AF XY: 0.808 AC XY: 59958 AN XY: 74194

African (AFR) AF: 0.414 AC: 17095 AN: 41342

American (AMR) AF: 0.908 AC: 13838 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.941 AC: 3259 AN: 3462

East Asian (EAS) AF: 0.784 AC: 4041 AN: 5154

South Asian (SAS) AF: 0.856 AC: 4131 AN: 4826

European-Finnish (FIN) AF: 0.980 AC: 10404 AN: 10614

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

European-Non Finnish (NFE) AF: 0.976 AC: 66201 AN: 67834

Other (OTH) AF: 0.834 AC: 1758 AN: 2108

Alfa AF: 0.879 Hom.: 9720

Bravo AF: 0.782

Asia WGS AF: 0.787 AC: 2732 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.68
DANN	Benign	0.64
PhyloP100		-0.32

Splicing

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

Other links and lift over

dbSNP: rs10734824; hg19: chr12-10414823;