12-10308289-C-T

Position:

• chr12-10308289-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002262.5(KLRD1):​c.7+205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 568,208 control chromosomes in the GnomAD database, including 272,169 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 0.94 (67393 hom., cov: 32)
  • Exomes 𝑓: 0.99 (204776 hom.)
• Consequence: KLRD1 NM_002262.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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]

KLRD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRD1	NM_002262.5	c.7+205C>T		intron_variant		ENST00000336164.9	NP_002253.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000336164.9	c.7+205C>T		intron_variant		1	NM_002262.5	ENSP00000338130.4

Frequencies

GnomAD3 genomes AF: 0.936 AC: 142343 AN: 152108 Hom.: 67365 Cov.: 32

Gnomad AFR AF: 0.776

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.977

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.975

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.951

GnomAD4 exome AF: 0.991 AC: 412418 AN: 415982 Hom.: 204776 Cov.: 4 AF XY: 0.993 AC XY: 218779 AN XY: 220314

Gnomad4 AFR exome AF: 0.774

Gnomad4 AMR exome AF: 0.984

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.999

Gnomad4 OTH exome AF: 0.982

GnomAD4 genome AF: 0.936 AC: 142423 AN: 152226 Hom.: 67393 Cov.: 32 AF XY: 0.938 AC XY: 69834 AN XY: 74436

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.977

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.952

Alfa AF: 0.961 Hom.: 8790

Bravo AF: 0.926

Asia WGS AF: 0.986 AC: 3429 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.22

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

Publications

LitVar

Other links and lift over

dbSNP: rs7301562; hg19: chr12-10460888;