rs11053720

Positions:

• chr12-10265806-A-G
• chr12-10265806-A-T

Variant summary

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

The XM_047429945.1(LOC124902875):​c.263-3106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,244 control chromosomes in the GnomAD database, including 1,998 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 0.13 (1998 hom., cov: 32)
• Consequence: LOC124902875 XM_047429945.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

Genes affected

LOC124902875 (HGNC:):

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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124902875	XM_047429945.1	c.263-3106T>C		intron_variant			XP_047285901.1
KLRD1	NM_001351060.2	c.-101+25066A>G		intron_variant			NP_001337989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000540271.1	n.169-38660A>G		intron_variant, non_coding_transcript_variant		1
KLRD1	ENST00000544747.5	c.-101+39573A>G		intron_variant		3		ENSP00000438669

Frequencies

GnomAD3 genomes AF: 0.125 AC: 19039 AN: 152124 Hom.: 1991 Cov.: 32

Gnomad AFR AF: 0.0282

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.125 AC: 19061 AN: 152244 Hom.: 1998 Cov.: 32 AF XY: 0.133 AC XY: 9915 AN XY: 74460

Gnomad4 AFR AF: 0.0281

Gnomad4 AMR AF: 0.255

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.143

Alfa AF: 0.124 Hom.: 1527

Bravo AF: 0.131

Asia WGS AF: 0.373 AC: 1293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.1
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11053720; hg19: chr12-10418405;