rs2617169

chr12-10408225-T-Achr12-10408225-T-G

Variant summary

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

The NM_013431.2(KLRC4):c.340+104A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 706,586 control chromosomes in the GnomAD database, including 236,803 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 0.83 (52509 hom., cov: 31)
  • Exomes 𝑓: 0.81 (184294 hom.)
• Consequence: KLRC4 NM_013431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLRC4	NM_013431.2	c.340+104A>T		intron_variant		ENST00000309384.3
KLRC4-KLRK1	NM_001199805.1	c.-335+104A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRC4	ENST00000309384.3	c.340+104A>T		intron_variant		1	NM_013431.2	P1

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126154 AN: 151950 Hom.: 52455 Cov.: 31

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.815

GnomAD4 exome AF: 0.814 AC: 451296 AN: 554518 Hom.: 184294 AF XY: 0.817 AC XY: 244842 AN XY: 299534

Gnomad4 AFR exome AF: 0.861

Gnomad4 AMR exome AF: 0.889

Gnomad4 ASJ exome AF: 0.800

Gnomad4 EAS exome AF: 0.792

Gnomad4 SAS exome AF: 0.877

Gnomad4 FIN exome AF: 0.808

Gnomad4 NFE exome AF: 0.801

Gnomad4 OTH exome AF: 0.804

GnomAD4 genome AF: 0.830 AC: 126270 AN: 152068 Hom.: 52509 Cov.: 31 AF XY: 0.831 AC XY: 61760 AN XY: 74324

Gnomad4 AFR AF: 0.861

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.803

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.810

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.817

Alfa AF: 0.788 Hom.: 2453

Bravo AF: 0.832

Asia WGS AF: 0.839 AC: 2907 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.12
Dann	Benign	0.15

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: rs2617169; hg19: chr12-10560824; COSMIC: COSV58672489; COSMIC: COSV58672489;