12-10388157-A-T

Position:

• chr12-10388157-A-T

Variant summary

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

The NM_007360.4(KLRK1):​c.40+614T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.171 in 152,108 control chromosomes in the GnomAD database, including 2,684 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 0.17 (2684 hom., cov: 32)
• Consequence: KLRK1 NM_007360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54

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:):

KLRK1-AS1 (HGNC:54868): (KLRK1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRK1	NM_007360.4	c.40+614T>A		intron_variant		ENST00000240618.11	NP_031386.2
KLRC4-KLRK1	NM_001199805.1	c.40+614T>A		intron_variant			NP_001186734.1
KLRK1-AS1	NR_120430.1	n.503-8022A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRK1	ENST00000240618.11	c.40+614T>A		intron_variant		1	NM_007360.4	ENSP00000240618	P1
KLRK1-AS1	ENST00000500682.1	n.503-8022A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25983 AN: 151992 Hom.: 2681 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.197

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.171 AC: 26012 AN: 152108 Hom.: 2684 Cov.: 32 AF XY: 0.174 AC XY: 12930 AN XY: 74354

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.197

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.133

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.161

Alfa AF: 0.146 Hom.: 220

Bravo AF: 0.176

Asia WGS AF: 0.259 AC: 892 AN: 3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.56
DANN	Benign	0.58

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: rs7962112; hg19: chr12-10540756;