12-10379727-T-C

Position:

chr12-10379727-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_007360.4(KLRK1):c.214A>G(p.Thr72Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.802 in 1,610,626 control chromosomes in the GnomAD database, including 520,524 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.75 ( 43298 hom., cov: 31)

Exomes 𝑓: 0.81 ( 477226 hom. )

Consequence

KLRK1
NM_007360.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.60

Variant links:

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]

KLRK1 links:

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]

KLRC4-KLRK1 links:

KLRK1-AS1 (HGNC:):

KLRK1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.0851428E-6).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRK1	NM_007360.4 linkuse as main transcript	c.214A>G	p.Thr72Ala	missense_variant	4/8	ENST00000240618.11	NP_031386.2	P26718-1A0A024RAP8
KLRC4-KLRK1	NM_001199805.1 linkuse as main transcript	c.214A>G	p.Thr72Ala	missense_variant	9/13		NP_001186734.1	P26718-1A0A024RAP8
KLRK1-AS1	NR_120430.1 linkuse as main transcript	n.393T>C		non_coding_transcript_exon_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLRK1	ENST00000240618.11 linkuse as main transcript	c.214A>G	p.Thr72Ala	missense_variant	4/8	1	NM_007360.4	ENSP00000240618.6	P26718-1
KLRC4-KLRK1	ENST00000539300.5 linkuse as main transcript	n.*411A>G		non_coding_transcript_exon_variant	9/13	2		ENSP00000455951.1	H3BQV0
KLRC4-KLRK1	ENST00000539300.5 linkuse as main transcript	n.*411A>G		3_prime_UTR_variant	9/13	2		ENSP00000455951.1	H3BQV0

Frequencies

GnomAD3 genomes

AF:

0.747

AC:

113519

AN:

151912

Hom.:

43277

Cov.:

show subpopulations

Gnomad AFR

AF:

0.577

Gnomad AMI

AF:

0.747

Gnomad AMR

AF:

0.828

Gnomad ASJ

AF:

0.796

Gnomad EAS

AF:

0.773

Gnomad SAS

AF:

0.884

Gnomad FIN

AF:

0.810

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.808

Gnomad OTH

AF:

0.760

GnomAD3 exomes

AF:

0.808

AC:

201579

AN:

249454

Hom.:

82203

AF XY:

0.812

AC XY:

109435

AN XY:

134778

show subpopulations

Gnomad AFR exome

AF:

0.576

Gnomad AMR exome

AF:

0.888

Gnomad ASJ exome

AF:

0.788

Gnomad EAS exome

AF:

0.759

Gnomad SAS exome

AF:

0.886

Gnomad FIN exome

AF:

0.810

Gnomad NFE exome

AF:

0.806

Gnomad OTH exome

AF:

0.801

GnomAD4 exome

AF:

0.807

AC:

1177745

AN:

1458596

Hom.:

477226

Cov.:

AF XY:

0.810

AC XY:

587957

AN XY:

725450

show subpopulations

Gnomad4 AFR exome

AF:

0.570

Gnomad4 AMR exome

AF:

0.882

Gnomad4 ASJ exome

AF:

0.789

Gnomad4 EAS exome

AF:

0.789

Gnomad4 SAS exome

AF:

0.880

Gnomad4 FIN exome

AF:

0.809

Gnomad4 NFE exome

AF:

0.808

Gnomad4 OTH exome

AF:

0.787

GnomAD4 genome

AF:

0.747

AC:

113585

AN:

152030

Hom.:

43298

Cov.:

AF XY:

0.749

AC XY:

55700

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.577

Gnomad4 AMR

AF:

0.828

Gnomad4 ASJ

AF:

0.796

Gnomad4 EAS

AF:

0.774

Gnomad4 SAS

AF:

0.884

Gnomad4 FIN

AF:

0.810

Gnomad4 NFE

AF:

0.808

Gnomad4 OTH

AF:

0.763

Alfa

AF:

0.795

Hom.:

125241

Bravo

AF:

0.738

TwinsUK

AF:

0.807

AC:

2994

ALSPAC

AF:

0.799

AC:

3080

ESP6500AA

AF:

0.579

AC:

2552

ESP6500EA

AF:

0.800

AC:

6877

ExAC

AF:

0.803

AC:

97496

Asia WGS

AF:

0.816

AC:

2836

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.87

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.3

DANN

Benign

0.91

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.30

.;T

MetaRNN

Benign

0.0000011

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.60

N;N

REVEL

Benign

0.010

Sift

Benign

0.96

T;T

Sift4G

Benign

0.27

T;T

Vest4

0.044

MPC

0.18

ClinPred

0.00087

GERP RS

-1.4

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over