rs1049174

Variant names:

• chr12-10372766-G-C
• rs1049174
• NM_007360.4:c.*348C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-10372766-G-C
• chr12-10372766-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.404
• Publications: 52 publications found

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:54868): (KLRK1 antisense RNA 1)

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007360.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRK1	NM_007360.4	MANE Select	c.*348C>G		3_prime_UTR	Exon 8 of 8	NP_031386.2
	KLRC4-KLRK1	NM_001199805.1		c.*348C>G		3_prime_UTR	Exon 13 of 13	NP_001186734.1
	KLRK1-AS1	NR_120430.1		n.266-1269G>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRK1	ENST00000240618.11	TSL:1 MANE Select	c.*348C>G		3_prime_UTR	Exon 8 of 8	ENSP00000240618.6
	KLRK1	ENST00000540267.5	TSL:5	n.1437C>G		non_coding_transcript_exon	Exon 5 of 5
	KLRC4-KLRK1	ENST00000543572.6	TSL:2	n.*1223C>G		non_coding_transcript_exon	Exon 10 of 10	ENSP00000456286.1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87525 AN: 151962 Hom.: 27495 Cov.: 32

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.: 0 AF XY: 0.646 AC XY: 39586 AN XY: 61326

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

GnomAD4 genome AF: 0.576 AC: 87560 AN: 152080 Hom.: 27506 Cov.: 32 AF XY: 0.575 AC XY: 42713 AN XY: 74344

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

Alfa AF: 0.534 Hom.: 1843

Bravo AF: 0.562

Asia WGS AF: 0.543 AC: 1890 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.45
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1049174; hg19: chr12-10525365;