12-10229491-T-G

Variant names:

• chr12-10229491-T-G
• rs10845076
• ENST00000540271.1:n.168+3258T>G

Variant summary

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

The ENST00000544747.5(KLRD1):​c.-101+3258T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.603 in 149,730 control chromosomes in the GnomAD database, including 32,326 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 0.60 (32326 hom., cov: 26)
• Consequence: KLRD1 ENST00000544747.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• 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]

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 (NFE) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000544747.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRD1	ENST00000540271.1	TSL:1	n.168+3258T>G		intron	N/A
	KLRD1	ENST00000544747.5	TSL:3	c.-101+3258T>G		intron	N/A	ENSP00000438669.1	F5H2B7

Frequencies

GnomAD3 genomes AF: 0.603 AC: 90261 AN: 149652 Hom.: 32340 Cov.: 26

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.909

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.721

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.802

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.816

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.603 AC: 90239 AN: 149730 Hom.: 32326 Cov.: 26 AF XY: 0.599 AC XY: 43620 AN XY: 72838

African (AFR) AF: 0.245 AC: 10012 AN: 40878

American (AMR) AF: 0.602 AC: 9025 AN: 14982

Ashkenazi Jewish (ASJ) AF: 0.721 AC: 2497 AN: 3464

East Asian (EAS) AF: 0.176 AC: 904 AN: 5128

South Asian (SAS) AF: 0.531 AC: 2534 AN: 4768

European-Finnish (FIN) AF: 0.802 AC: 7669 AN: 9558

Middle Eastern (MID) AF: 0.781 AC: 225 AN: 288

European-Non Finnish (NFE) AF: 0.816 AC: 55248 AN: 67674

Other (OTH) AF: 0.624 AC: 1298 AN: 2080

Alfa AF: 0.709 Hom.: 6131

Bravo AF: 0.575

Asia WGS AF: 0.332 AC: 1155 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.0
DANN	Benign	0.68
PhyloP100		0.080

Splicing

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

Other links and lift over

dbSNP: rs10845076; hg19: chr12-10382090;