NM_002259.5:c.489+146G>A

Variant names:

• chr12-10449091-C-T
• rs7301582
• NM_002259.5:c.489+146G>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.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
• Publications: 14 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 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.489+146G>A		intron	N/A	NP_002250.2
	KLRC1	NM_213658.3		c.489+146G>A		intron	N/A	NP_998823.2
	KLRC1	NM_001304448.1		c.489+146G>A		intron	N/A	NP_001291377.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC1	ENST00000359151.8	TSL:1 MANE Select	c.489+146G>A		intron	N/A	ENSP00000352064.3
	KLRC1	ENST00000544822.2	TSL:1	c.489+146G>A		intron	N/A	ENSP00000438038.1
	KLRC1	ENST00000536188.5	TSL:1	c.489+146G>A		intron	N/A	ENSP00000441432.1

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

African (AFR) AF: 0.489 AC: 10059 AN: 20560

American (AMR) AF: 0.174 AC: 3647 AN: 20992

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 3360 AN: 16906

East Asian (EAS) AF: 0.108 AC: 3581 AN: 33258

South Asian (SAS) AF: 0.148 AC: 8249 AN: 55686

European-Finnish (FIN) AF: 0.202 AC: 8896 AN: 44108

Middle Eastern (MID) AF: 0.205 AC: 758 AN: 3702

European-Non Finnish (NFE) AF: 0.212 AC: 146340 AN: 691870

Other (OTH) AF: 0.227 AC: 9310 AN: 41080

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

African (AFR) AF: 0.491 AC: 20346 AN: 41426

American (AMR) AF: 0.202 AC: 3088 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 697 AN: 3466

East Asian (EAS) AF: 0.142 AC: 737 AN: 5186

South Asian (SAS) AF: 0.143 AC: 690 AN: 4824

European-Finnish (FIN) AF: 0.206 AC: 2184 AN: 10586

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.218 AC: 14796 AN: 67962

Other (OTH) AF: 0.268 AC: 566 AN: 2114

Alfa AF: 0.244 Hom.: 3339

Bravo AF: 0.297

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.20
PhyloP100		-1.4
PromoterAI		-0.0046	Neutral
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: rs7301582; hg19: chr12-10601690;