chr12-10262224-A-G

Position:

• chr12-10262224-A-G

Variant summary

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

The XM_047429945.1(LOC124902875):​c.*86T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 151,790 control chromosomes in the GnomAD database, including 53,485 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 0.80 (53485 hom., cov: 32)
• Consequence: LOC124902875 XM_047429945.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.323

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC124902875	XM_047429945.1	c.*86T>C		3_prime_UTR_variant	5/5
KLRD1	NM_001351060.2	c.-101+21484A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRD1	ENST00000540271.1	n.168+35991A>G		intron_variant, non_coding_transcript_variant		1
KLRD1	ENST00000544747.5	c.-101+35991A>G		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.804 AC: 121887 AN: 151674 Hom.: 53485 Cov.: 32

Gnomad AFR AF: 0.414

Gnomad AMI AF: 0.991

Gnomad AMR AF: 0.907

Gnomad ASJ AF: 0.941

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.856

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.976

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.803 AC: 121907 AN: 151790 Hom.: 53485 Cov.: 32 AF XY: 0.808 AC XY: 59958 AN XY: 74194

Gnomad4 AFR AF: 0.414

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.941

Gnomad4 EAS AF: 0.784

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.976

Gnomad4 OTH AF: 0.834

Alfa AF: 0.879 Hom.: 9720

Bravo AF: 0.782

Asia WGS AF: 0.787 AC: 2732 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.68
DANN	Benign	0.64

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10734824; hg19: chr12-10414823;