rs2734414

Variant names:

• chr12-10446203-A-T
• rs2734414
• NM_002259.5:c.*348T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002259.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC1	NM_002259.5	MANE Select	c.*348T>A		3_prime_UTR	Exon 7 of 7	NP_002250.2	P26715-1
	KLRC1	NM_213658.3		c.*348T>A		3_prime_UTR	Exon 8 of 8	NP_998823.2	P26715-1
	KLRC1	NM_007328.4		c.*348T>A		3_prime_UTR	Exon 6 of 6	NP_015567.2	P26715-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC1	ENST00000359151.8	TSL:1 MANE Select	c.*348T>A		3_prime_UTR	Exon 7 of 7	ENSP00000352064.3	P26715-1
	KLRC1	ENST00000544822.2	TSL:1	c.*348T>A		3_prime_UTR	Exon 8 of 8	ENSP00000438038.1	P26715-1
	KLRC1	ENST00000347831.9	TSL:1	c.*348T>A		3_prime_UTR	Exon 6 of 6	ENSP00000256965.7	P26715-2

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

African (AFR) AF: 0.602 AC: 850 AN: 1412

American (AMR) AF: 0.297 AC: 1087 AN: 3662

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 287 AN: 1576

East Asian (EAS) AF: 0.381 AC: 1023 AN: 2684

South Asian (SAS) AF: 0.338 AC: 2597 AN: 7682

European-Finnish (FIN) AF: 0.192 AC: 438 AN: 2280

Middle Eastern (MID) AF: 0.180 AC: 49 AN: 272

European-Non Finnish (NFE) AF: 0.160 AC: 11121 AN: 69700

Other (OTH) AF: 0.221 AC: 917 AN: 4154

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

African (AFR) AF: 0.620 AC: 25697 AN: 41424

American (AMR) AF: 0.279 AC: 4259 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.207 AC: 717 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2129 AN: 5168

South Asian (SAS) AF: 0.384 AC: 1851 AN: 4822

European-Finnish (FIN) AF: 0.227 AC: 2400 AN: 10558

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12877 AN: 67962

Other (OTH) AF: 0.299 AC: 630 AN: 2104

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.78
DANN	Benign	0.42
PhyloP100		-0.28
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: rs2734414; hg19: chr12-10598802;