rs17513986

Positions:

• chr12-10408105-A-C

Variant summary

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

The NM_013431.2(KLRC4):​c.340+224T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 152,176 control chromosomes in the GnomAD database, including 838 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 0.10 (838 hom., cov: 32)
• Consequence: KLRC4 NM_013431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC4	NM_013431.2	c.340+224T>G		intron_variant		ENST00000309384.3	NP_038459.1
KLRC4-KLRK1	NM_001199805.1	c.-335+224T>G		intron_variant			NP_001186734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRC4	ENST00000309384.3	c.340+224T>G		intron_variant		1	NM_013431.2	ENSP00000310216.1
KLRC4-KLRK1	ENST00000539300.5	n.313+224T>G		intron_variant		2		ENSP00000455951.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15510 AN: 152058 Hom.: 838 Cov.: 32

Gnomad AFR AF: 0.0815

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0730

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.0294

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.102 AC: 15517 AN: 152176 Hom.: 838 Cov.: 32 AF XY: 0.101 AC XY: 7520 AN XY: 74390

Gnomad4 AFR AF: 0.0816

Gnomad4 AMR AF: 0.0729

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.0652

Gnomad4 FIN AF: 0.123

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.116

Alfa AF: 0.120 Hom.: 133

Bravo AF: 0.0973

Asia WGS AF: 0.0650 AC: 224 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.4
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: rs17513986; hg19: chr12-10560704;