rs2734565

Positions:

• chr12-10407992-C-T

Variant summary

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

The NM_013431.2(KLRC4):​c.341-203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 151,918 control chromosomes in the GnomAD database, including 36,545 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 0.69 (36545 hom., cov: 31)
• Consequence: KLRC4 NM_013431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.19

Genes affected

KLRC4 (HGNC:6377): (killer cell lectin like receptor C4) 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. This gene is a member of the NKG2 group of genes that are expressed primarily in natural killer (NK) cells. These family members encode transmembrane proteins that are characterized by a type II membrane orientation (have an extracellular C-terminus) and the presence of a C-type lectin domain. This family member is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed in NK cells. Read-through transcription exists between this gene and the downstream KLRK1 (killer cell lectin-like receptor subfamily K, member 1) family member. [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]

KLRC4-KLRK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC4	NM_013431.2	c.341-203G>A		intron_variant		ENST00000309384.3	NP_038459.1
KLRC4-KLRK1	NM_001199805.1	c.-334-203G>A		intron_variant			NP_001186734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRC4	ENST00000309384.3	c.341-203G>A		intron_variant		1	NM_013431.2	ENSP00000310216.1
KLRC4-KLRK1	ENST00000539300.5	n.314-203G>A		intron_variant		2		ENSP00000455951.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105093 AN: 151798 Hom.: 36512 Cov.: 31

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.780

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.688

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.667

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

GnomAD4 genome AF: 0.692 AC: 105184 AN: 151918 Hom.: 36545 Cov.: 31 AF XY: 0.695 AC XY: 51617 AN XY: 74256

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.780

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.738

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.688

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.671

Alfa AF: 0.698 Hom.: 21018

Bravo AF: 0.694

Asia WGS AF: 0.770 AC: 2676 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.48

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: rs2734565; hg19: chr12-10560591;