12-10449478-C-G

Variant names:

• chr12-10449478-C-G
• rs2734440
• NM_002259.5:c.338-90G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002259.5(KLRC1):​c.338-90G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLRC1 NM_002259.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.63
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

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>C		intron	N/A	NP_002250.2
	KLRC1	NM_213658.3		c.338-90G>C		intron	N/A	NP_998823.2
	KLRC1	NM_001304448.1		c.338-90G>C		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>C		intron	N/A	ENSP00000352064.3
	KLRC1	ENST00000544822.2	TSL:1	c.338-90G>C		intron	N/A	ENSP00000438038.1
	KLRC1	ENST00000536188.5	TSL:1	c.338-90G>C		intron	N/A	ENSP00000441432.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1402380 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 693390

African (AFR) AF: 0.00 AC: 0 AN: 31248

American (AMR) AF: 0.00 AC: 0 AN: 36146

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39336

South Asian (SAS) AF: 0.00 AC: 0 AN: 74484

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50882

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5434

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1084740

Other (OTH) AF: 0.00 AC: 0 AN: 58006

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.14
DANN	Benign	0.38
PhyloP100		-1.6
PromoterAI		-0.029	Neutral

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;