rs17513986

Variant names:

• chr12-10408105-A-C
• rs17513986
• NM_013431.2:c.340+224T>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013431.2. 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
	KLRC4	NM_013431.2	MANE Select	c.340+224T>G		intron	N/A	NP_038459.1
	KLRC4-KLRK1	NM_001199805.1		c.-335+224T>G		intron	N/A	NP_001186734.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC4	ENST00000309384.3	TSL:1 MANE Select	c.340+224T>G		intron	N/A	ENSP00000310216.1
	KLRC4-KLRK1	ENST00000539300.5	TSL:2	n.313+224T>G		intron	N/A	ENSP00000455951.1
	KLRC4	ENST00000718241.1		c.340+224T>G		intron	N/A	ENSP00000520686.1

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

African (AFR) AF: 0.0816 AC: 3389 AN: 41528

American (AMR) AF: 0.0729 AC: 1114 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.191 AC: 661 AN: 3468

East Asian (EAS) AF: 0.0297 AC: 154 AN: 5186

South Asian (SAS) AF: 0.0652 AC: 315 AN: 4828

European-Finnish (FIN) AF: 0.123 AC: 1302 AN: 10584

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8191 AN: 67994

Other (OTH) AF: 0.116 AC: 244 AN: 2110

Alfa AF: 0.119 Hom.: 133

Bravo AF: 0.0973

Asia WGS AF: 0.0650 AC: 224 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.4
DANN	Benign	0.58
PhyloP100		1.4
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: rs17513986; hg19: chr12-10560704;