12-10265806-A-G

Variant names:

• chr12-10265806-A-G
• rs11053720
• ENST00000540271.1:n.169-38660A>G

Variant summary

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

The ENST00000540271.1(KLRD1):​n.169-38660A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,244 control chromosomes in the GnomAD database, including 1,998 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 0.13 (1998 hom., cov: 32)
• Consequence: KLRD1 ENST00000540271.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000540271.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRD1	NM_001351060.2		c.-101+25066A>G		intron	N/A	NP_001337989.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRD1	ENST00000540271.1	TSL:1	n.169-38660A>G		intron	N/A
	KLRD1	ENST00000544747.5	TSL:3	c.-101+39573A>G		intron	N/A	ENSP00000438669.1
	ENSG00000309652	ENST00000842798.1		n.128-3106T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19039 AN: 152124 Hom.: 1991 Cov.: 32

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.125 AC: 19061 AN: 152244 Hom.: 1998 Cov.: 32 AF XY: 0.133 AC XY: 9915 AN XY: 74460

African (AFR) AF: 0.0281 AC: 1170 AN: 41570

American (AMR) AF: 0.255 AC: 3891 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3472

East Asian (EAS) AF: 0.448 AC: 2324 AN: 5182

South Asian (SAS) AF: 0.297 AC: 1433 AN: 4826

European-Finnish (FIN) AF: 0.115 AC: 1220 AN: 10604

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7933 AN: 68000

Other (OTH) AF: 0.143 AC: 303 AN: 2112

Alfa AF: 0.123 Hom.: 2858

Bravo AF: 0.131

Asia WGS AF: 0.373 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.67
PhyloP100		1.4

Splicing

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

Other links and lift over

dbSNP: rs11053720; hg19: chr12-10418405;