chr12-10309917-C-T

Variant names:

• chr12-10309917-C-T
• rs2270238
• NM_002262.5:c.163+229C>T

Variant summary

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

The NM_001351060.2(KLRD1):​c.163+229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,024 control chromosomes in the GnomAD database, including 5,183 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 0.24 (5183 hom., cov: 32)
• Consequence: KLRD1 NM_001351060.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.963
• 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRD1	NM_002262.5	MANE Select	c.163+229C>T		intron	N/A	NP_002253.2
	KLRD1	NM_001351060.2		c.163+229C>T		intron	N/A	NP_001337989.1
	KLRD1	NM_001414224.1		c.163+229C>T		intron	N/A	NP_001401153.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRD1	ENST00000336164.9	TSL:1 MANE Select	c.163+229C>T		intron	N/A	ENSP00000338130.4
	KLRD1	ENST00000381908.7	TSL:1	c.163+229C>T		intron	N/A	ENSP00000371333.4
	KLRD1	ENST00000543777.5	TSL:1	c.100+437C>T		intron	N/A	ENSP00000443584.1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35825 AN: 151906 Hom.: 5179 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.320

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.236 AC: 35840 AN: 152024 Hom.: 5183 Cov.: 32 AF XY: 0.242 AC XY: 17984 AN XY: 74294

African (AFR) AF: 0.0624 AC: 2587 AN: 41474

American (AMR) AF: 0.328 AC: 5005 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3470

East Asian (EAS) AF: 0.320 AC: 1660 AN: 5180

South Asian (SAS) AF: 0.257 AC: 1238 AN: 4812

European-Finnish (FIN) AF: 0.339 AC: 3563 AN: 10518

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20118 AN: 67976

Other (OTH) AF: 0.235 AC: 497 AN: 2112

Alfa AF: 0.276 Hom.: 18402

Bravo AF: 0.228

Asia WGS AF: 0.278 AC: 965 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.44
DANN	Benign	0.61
PhyloP100		-0.96
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: rs2270238; hg19: chr12-10462516;