chr12-10314468-A-G

Variant names:

• chr12-10314468-A-G
• rs11611333
• NM_002262.5:c.420-205A>G

Variant summary

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

The NM_002262.5(KLRD1):​c.420-205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,942 control chromosomes in the GnomAD database, including 12,699 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 0.41 (12699 hom., cov: 32)
• Consequence: KLRD1 NM_002262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRD1	NM_002262.5	c.420-205A>G		intron_variant	Intron 5 of 5	ENST00000336164.9	NP_002253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000336164.9	c.420-205A>G		intron_variant	Intron 5 of 5	1	NM_002262.5	ENSP00000338130.4

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61764 AN: 151824 Hom.: 12683 Cov.: 32

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.499

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.424

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.407 AC: 61832 AN: 151942 Hom.: 12699 Cov.: 32 AF XY: 0.409 AC XY: 30384 AN XY: 74246

African (AFR) AF: 0.400 AC: 16594 AN: 41438

American (AMR) AF: 0.466 AC: 7121 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1417 AN: 3470

East Asian (EAS) AF: 0.499 AC: 2579 AN: 5166

South Asian (SAS) AF: 0.323 AC: 1555 AN: 4816

European-Finnish (FIN) AF: 0.424 AC: 4470 AN: 10536

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26860 AN: 67924

Other (OTH) AF: 0.421 AC: 891 AN: 2116

Alfa AF: 0.402 Hom.: 46247

Bravo AF: 0.411

Asia WGS AF: 0.398 AC: 1383 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.69
DANN	Benign	0.44
PhyloP100		-0.32
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: rs11611333; hg19: chr12-10467067; COSMIC: COSV60273541; COSMIC: COSV60273541;