chr12-10372766-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_007360.4(KLRK1):c.*348C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.611 in 263,650 control chromosomes in the GnomAD database, including 52,117 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 27506 hom., cov: 32)

Exomes 𝑓: 0.66 ( 24611 hom. )

Consequence

KLRK1
NM_007360.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.404

Publications

52 publications found

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:54868): (KLRK1 antisense RNA 1)

KLRK1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-10372766-G-C is Benign according to our data. Variant chr12-10372766-G-C is described in ClinVar as Benign. ClinVar VariationId is 1238157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
KLRK1	NM_007360.4 link	c.*348C>G	3_prime_UTR_variant	Exon 8 of 8	ENST00000240618.11	NP_031386.2	P26718-1A0A024RAP8
KLRC4-KLRK1	NM_001199805.1 link	c.*348C>G	3_prime_UTR_variant	Exon 13 of 13		NP_001186734.1	P26718-1A0A024RAP8
KLRK1-AS1	NR_120430.1 link	n.266-1269G>C	intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRK1	ENST00000240618.11 link	c.*348C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_007360.4	ENSP00000240618.6		P26718-1
KLRC4-KLRK1	ENST00000539300.5 link	n.*1196C>G		downstream_gene_variant		2		ENSP00000455951.1		H3BQV0

Frequencies

GnomAD3 genomes

AF:

0.576

AC:

87525

AN:

151962

Hom.:

27495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.651

Gnomad AMR

AF:

0.659

Gnomad ASJ

AF:

0.601

Gnomad EAS

AF:

0.568

Gnomad SAS

AF:

0.555

Gnomad FIN

AF:

0.677

Gnomad MID

AF:

0.589

Gnomad NFE

AF:

0.706

Gnomad OTH

AF:

0.600

GnomAD4 exome

AF:

0.658

AC:

73420

AN:

111570

Hom.:

24611

Cov.:

AF XY:

0.646

AC XY:

39586

AN XY:

61326

show subpopulations

African (AFR)

AF:

0.315

AC:

319

AN:

1014

American (AMR)

AF:

0.645

AC:

628

AN:

974

Ashkenazi Jewish (ASJ)

AF:

0.602

AC:

1620

AN:

2690

East Asian (EAS)

AF:

0.585

AC:

669

AN:

1144

South Asian (SAS)

AF:

0.557

AC:

12173

AN:

21864

European-Finnish (FIN)

AF:

0.671

AC:

4495

AN:

6700

Middle Eastern (MID)

AF:

0.574

AC:

288

AN:

502

European-Non Finnish (NFE)

AF:

0.698

AC:

49273

AN:

70566

Other (OTH)

AF:

0.647

AC:

3955

AN:

6116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1120

2240

3359

4479

5599

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

216

288

360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.576

AC:

87560

AN:

152080

Hom.:

27506

Cov.:

AF XY:

0.575

AC XY:

42713

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.304

AC:

12614

AN:

41468

American (AMR)

AF:

0.659

AC:

10081

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.601

AC:

2084

AN:

3470

East Asian (EAS)

AF:

0.568

AC:

2924

AN:

5152

South Asian (SAS)

AF:

0.556

AC:

2682

AN:

4828

European-Finnish (FIN)

AF:

0.677

AC:

7151

AN:

10564

Middle Eastern (MID)

AF:

0.595

AC:

175

AN:

294

European-Non Finnish (NFE)

AF:

0.706

AC:

47984

AN:

67984

Other (OTH)

AF:

0.603

AC:

1273

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1690

3380

5071

6761

8451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

728

1456

2184

2912

3640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.534

Hom.:

1843

Bravo

AF:

0.562

Asia WGS

AF:

0.543

AC:

1890

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jan 18, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 27995954) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

2.6

(source)

DANN

Benign

0.45

PhyloP100

0.40

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over