12-10384670-C-T

Position:

• chr12-10384670-C-T

Variant summary

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

The NM_007360.4(KLRK1):​c.148+2233G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,822 control chromosomes in the GnomAD database, including 14,011 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 0.41 (14011 hom., cov: 32)
• Consequence: KLRK1 NM_007360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720

Genes affected

KLRK1 (HGNC:18788): (killer cell lectin like receptor K1) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. The NKG2 gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed in NK cells. This gene encodes a member of the NKG2 family. The encoded transmembrane protein is characterized by a type II membrane orientation (has an extracellular C terminus) and the presence of a C-type lectin domain. It binds to a diverse family of ligands that include MHC class I chain-related A and B proteins and UL-16 binding proteins, where ligand-receptor interactions can result in the activation of NK and T cells. The surface expression of these ligands is important for the recognition of stressed cells by the immune system, and thus this protein and its ligands are therapeutic targets for the treatment of immune diseases and cancers. Read-through transcription exists between this gene and the upstream KLRC4 (killer cell lectin-like receptor subfamily C, member 4) family member in the same cluster. [provided by RefSeq, Dec 2010]

KLRC4-KLRK1 (HGNC:48357): (KLRC4-KLRK1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring KLRC4 (killer cell lectin-like receptor subfamily C, member 4) and KLRK1 (killer cell lectin-like receptor subfamily K, member 1) genes on chromosome 12. The read-through transcript includes an alternate 5' exon and lacks a significant portion of the KLRC4 coding sequence, including the start codon, and it thus encodes the KLRK1 protein. [provided by RefSeq, Dec 2010]

KLRK1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRK1	NM_007360.4	c.148+2233G>A		intron_variant		ENST00000240618.11	NP_031386.2
KLRC4-KLRK1	NM_001199805.1	c.148+2233G>A		intron_variant			NP_001186734.1
KLRK1-AS1	NR_120430.1	n.502+4834C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRK1	ENST00000240618.11	c.148+2233G>A		intron_variant		1	NM_007360.4	ENSP00000240618.6
KLRC4-KLRK1	ENST00000539300.5	n.*345+2233G>A		intron_variant		2		ENSP00000455951.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62541 AN: 151704 Hom.: 13999 Cov.: 32

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.378

Gnomad NFE AF: 0.478

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.412 AC: 62573 AN: 151822 Hom.: 14011 Cov.: 32 AF XY: 0.415 AC XY: 30776 AN XY: 74186

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.543

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.513

Gnomad4 NFE AF: 0.478

Gnomad4 OTH AF: 0.425

Alfa AF: 0.467 Hom.: 34067

Bravo AF: 0.405

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.85
DANN	Benign	0.46

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: rs11053781; hg19: chr12-10537269;