chr12-10318451-A-G

Position:

• chr12-10318451-A-G

Variant summary

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

The NM_002262.5(KLRD1):​c.*3658A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,032 control chromosomes in the GnomAD database, including 28,161 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 0.58 (28161 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: KLRD1 NM_002262.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.239

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLRD1	NM_002262.5	c.*3658A>G		3_prime_UTR_variant	6/6	ENST00000336164.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRD1	ENST00000336164.9	c.*3658A>G		3_prime_UTR_variant	6/6	1	NM_002262.5	P1
KLRD1	ENST00000381908.7	c.*3658A>G		3_prime_UTR_variant	7/7	1		P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88583 AN: 151914 Hom.: 28144 Cov.: 31

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.770

Gnomad AMR AF: 0.739

Gnomad ASJ AF: 0.678

Gnomad EAS AF: 0.775

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.607

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.583 AC: 88631 AN: 152032 Hom.: 28161 Cov.: 31 AF XY: 0.590 AC XY: 43869 AN XY: 74318

Gnomad4 AFR AF: 0.313

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.678

Gnomad4 EAS AF: 0.775

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.664

Gnomad4 OTH AF: 0.612

Alfa AF: 0.615 Hom.: 3938

Bravo AF: 0.577

Asia WGS AF: 0.789 AC: 2741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.8
DANN	Benign	0.55

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: rs12303914; hg19: chr12-10471050;