NM_002259.5:c.338-90G>A

Variant names:

• chr12-10449478-C-T
• rs2734440
• NM_002259.5:c.338-90G>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.338-90G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.624 in 1,553,716 control chromosomes in the GnomAD database, including 309,028 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 0.53 (23810 hom., cov: 32)
  • Exomes 𝑓: 0.63 (285218 hom.)
• Consequence: KLRC1 NM_002259.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 16 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 (NFE) allele frequency at 95% confidence interval = 0.645 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC1	NM_002259.5	MANE Select	c.338-90G>A		intron	N/A	NP_002250.2
	KLRC1	NM_213658.3		c.338-90G>A		intron	N/A	NP_998823.2
	KLRC1	NM_001304448.1		c.338-90G>A		intron	N/A	NP_001291377.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC1	ENST00000359151.8	TSL:1 MANE Select	c.338-90G>A		intron	N/A	ENSP00000352064.3
	KLRC1	ENST00000544822.2	TSL:1	c.338-90G>A		intron	N/A	ENSP00000438038.1
	KLRC1	ENST00000536188.5	TSL:1	c.338-90G>A		intron	N/A	ENSP00000441432.1

Frequencies

GnomAD3 genomes AF: 0.534 AC: 81146 AN: 151914 Hom.: 23804 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.637

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.549

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.553

GnomAD4 exome AF: 0.634 AC: 888770 AN: 1401684 Hom.: 285218 AF XY: 0.633 AC XY: 438556 AN XY: 693022

African (AFR) AF: 0.258 AC: 8057 AN: 31232

American (AMR) AF: 0.593 AC: 21408 AN: 36104

Ashkenazi Jewish (ASJ) AF: 0.603 AC: 13325 AN: 22094

East Asian (EAS) AF: 0.645 AC: 25371 AN: 39318

South Asian (SAS) AF: 0.552 AC: 41099 AN: 74454

European-Finnish (FIN) AF: 0.638 AC: 32423 AN: 50854

Middle Eastern (MID) AF: 0.602 AC: 3267 AN: 5430

European-Non Finnish (NFE) AF: 0.654 AC: 709011 AN: 1084214

Other (OTH) AF: 0.600 AC: 34809 AN: 57984

GnomAD4 genome AF: 0.534 AC: 81174 AN: 152032 Hom.: 23810 Cov.: 32 AF XY: 0.535 AC XY: 39788 AN XY: 74336

African (AFR) AF: 0.271 AC: 11218 AN: 41470

American (AMR) AF: 0.610 AC: 9323 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2069 AN: 3470

East Asian (EAS) AF: 0.617 AC: 3193 AN: 5178

South Asian (SAS) AF: 0.549 AC: 2647 AN: 4820

European-Finnish (FIN) AF: 0.630 AC: 6642 AN: 10546

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44163 AN: 67948

Other (OTH) AF: 0.556 AC: 1175 AN: 2114

Alfa AF: 0.501 Hom.: 5543

Bravo AF: 0.518

Asia WGS AF: 0.572 AC: 1991 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	0.19
DANN	Benign	0.37
PhyloP100		-1.6
PromoterAI		-0.026	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: rs2734440; hg19: chr12-10602077; COSMIC: COSV61726021; COSMIC: COSV61726021;