rs3759270

Variant names:

• chr12-10306592-G-A
• rs3759270
• ENST00000381908.7:c.-100-1386G>A

Variant summary

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

The NM_001351060.2(KLRD1):​c.-100-1386G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 152,052 control chromosomes in the GnomAD database, including 31,320 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 0.64 (31320 hom., cov: 32)
• Consequence: KLRD1 NM_001351060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 3 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=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001351060.2. 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
	KLRD1	NM_001351060.2		c.-100-1386G>A		intron	N/A	NP_001337989.1
	KLRD1	NM_001114396.3		c.-100-1386G>A		intron	N/A	NP_001107868.2	Q13241-1
	KLRD1	NM_001351062.2		c.-101+360G>A		intron	N/A	NP_001337991.1	Q13241-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRD1	ENST00000381908.7	TSL:1	c.-100-1386G>A		intron	N/A	ENSP00000371333.4	Q13241-1
	KLRD1	ENST00000540271.1	TSL:1	n.251-1386G>A		intron	N/A
	KLRD1	ENST00000862987.1		c.-101+360G>A		intron	N/A	ENSP00000533046.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97384 AN: 151934 Hom.: 31308 Cov.: 32

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.754

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.675

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.645

Gnomad OTH AF: 0.647

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

GnomAD4 genome AF: 0.641 AC: 97436 AN: 152052 Hom.: 31320 Cov.: 32 AF XY: 0.637 AC XY: 47341 AN XY: 74336

African (AFR) AF: 0.665 AC: 27594 AN: 41472

American (AMR) AF: 0.601 AC: 9181 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.675 AC: 2341 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2652 AN: 5176

South Asian (SAS) AF: 0.675 AC: 3254 AN: 4820

European-Finnish (FIN) AF: 0.600 AC: 6333 AN: 10562

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.645 AC: 43820 AN: 67964

Other (OTH) AF: 0.650 AC: 1371 AN: 2110

Alfa AF: 0.648 Hom.: 16332

Bravo AF: 0.641

Asia WGS AF: 0.605 AC: 2104 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3759270; hg19: chr12-10459191;