rs7301582

Positions:

• chr12-10449091-C-T

Variant summary

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

The NM_002259.5(KLRC1):​c.489+146G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,080,208 control chromosomes in the GnomAD database, including 29,386 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 0.29 (7434 hom., cov: 33)
  • Exomes 𝑓: 0.21 (21952 hom.)
• Consequence: KLRC1 NM_002259.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

Genes affected

KLRC1 (HGNC:6374): (killer cell lectin like receptor C1) 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. The protein encoded by this gene belongs to the killer cell lectin-like receptor family, also called NKG2 family, which is a group of transmembrane proteins preferentially expressed in NK cells. This family of proteins is characterized by the type II membrane orientation and the presence of a C-type lectin domain. This protein forms a complex with another family member, KLRD1/CD94, and has been implicated in the recognition of the MHC class I HLA-E molecules in NK cells. The genes of NKG2 family members form a killer cell lectin-like receptor gene cluster on chromosome 12. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jan 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC1	NM_002259.5	c.489+146G>A		intron_variant		ENST00000359151.8	NP_002250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRC1	ENST00000359151.8	c.489+146G>A		intron_variant		1	NM_002259.5	ENSP00000352064	P1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43338 AN: 151928 Hom.: 7411 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.143

Gnomad SAS AF: 0.143

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.271

GnomAD4 exome AF: 0.209 AC: 194200 AN: 928162 Hom.: 21952 AF XY: 0.206 AC XY: 96174 AN XY: 466544

Gnomad4 AFR exome AF: 0.489

Gnomad4 AMR exome AF: 0.174

Gnomad4 ASJ exome AF: 0.199

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.148

Gnomad4 FIN exome AF: 0.202

Gnomad4 NFE exome AF: 0.212

Gnomad4 OTH exome AF: 0.227

GnomAD4 genome AF: 0.285 AC: 43407 AN: 152046 Hom.: 7434 Cov.: 33 AF XY: 0.281 AC XY: 20878 AN XY: 74332

Gnomad4 AFR AF: 0.491

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.218

Gnomad4 OTH AF: 0.268

Alfa AF: 0.229 Hom.: 1956

Bravo AF: 0.297

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.20

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: rs7301582; hg19: chr12-10601690;