rs2734414

Positions:

• chr12-10446203-A-T

Variant summary

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

The NM_002259.5(KLRC1):​c.*348T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 245,414 control chromosomes in the GnomAD database, including 13,307 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 0.33 (11122 hom., cov: 31)
  • Exomes 𝑓: 0.20 (2185 hom.)
• Consequence: KLRC1 NM_002259.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC1	NM_002259.5	c.*348T>A		3_prime_UTR_variant	7/7	ENST00000359151.8	NP_002250.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRC1	ENST00000359151.8	c.*348T>A		3_prime_UTR_variant	7/7	1	NM_002259.5	ENSP00000352064	P1

Frequencies

GnomAD3 genomes AF: 0.334 AC: 50774 AN: 151874 Hom.: 11088 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.207

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.301

GnomAD4 exome AF: 0.197 AC: 18369 AN: 93422 Hom.: 2185 Cov.: 4 AF XY: 0.202 AC XY: 9567 AN XY: 47426

Gnomad4 AFR exome AF: 0.602

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.182

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.338

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.221

GnomAD4 genome AF: 0.335 AC: 50862 AN: 151992 Hom.: 11122 Cov.: 31 AF XY: 0.337 AC XY: 25034 AN XY: 74292

Gnomad4 AFR AF: 0.620

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.207

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.299

Alfa AF: 0.266 Hom.: 905

Bravo AF: 0.351

Asia WGS AF: 0.386 AC: 1340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.42

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: rs2734414; hg19: chr12-10598802;