rs2617169

Variant names:

• chr12-10408225-T-A
• rs2617169
• NM_013431.2:c.340+104A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-10408225-T-A
• chr12-10408225-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013431.2(KLRC4):​c.340+104A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 706,586 control chromosomes in the GnomAD database, including 236,803 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 0.83 (52509 hom., cov: 31)
  • Exomes 𝑓: 0.81 (184294 hom.)
• Consequence: KLRC4 NM_013431.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 8 publications found

Genes affected

KLRC4 (HGNC:6377): (killer cell lectin like receptor C4) 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. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. This gene is a member of the NKG2 group of genes that are expressed primarily in natural killer (NK) cells. These family members encode transmembrane proteins that are characterized by a type II membrane orientation (have an extracellular C-terminus) and the presence of a C-type lectin domain. This family member is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed in NK cells. Read-through transcription exists between this gene and the downstream KLRK1 (killer cell lectin-like receptor subfamily K, member 1) family member. [provided by RefSeq, Dec 2010]

KLRC4-KLRK1 (HGNC:48357): (KLRC4-KLRK1 readthrough) This locus represents naturally occurring read-through transcription between the neighboring KLRC4 (killer cell lectin-like receptor subfamily C, member 4) and KLRK1 (killer cell lectin-like receptor subfamily K, member 1) genes on chromosome 12. The read-through transcript includes an alternate 5' exon and lacks a significant portion of the KLRC4 coding sequence, including the start codon, and it thus encodes the KLRK1 protein. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC4	NM_013431.2	c.340+104A>T		intron_variant	Intron 3 of 3	ENST00000309384.3	NP_038459.1
KLRC4-KLRK1	NM_001199805.1	c.-335+104A>T		intron_variant	Intron 3 of 12		NP_001186734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC4	ENST00000309384.3	c.340+104A>T		intron_variant	Intron 3 of 3	1	NM_013431.2	ENSP00000310216.1
KLRC4-KLRK1	ENST00000539300.5	n.313+104A>T		intron_variant	Intron 3 of 12	2		ENSP00000455951.1

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126154 AN: 151950 Hom.: 52455 Cov.: 31

Gnomad AFR AF: 0.861

Gnomad AMI AF: 0.747

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.885

Gnomad FIN AF: 0.810

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.815

GnomAD4 exome AF: 0.814 AC: 451296 AN: 554518 Hom.: 184294 AF XY: 0.817 AC XY: 244842 AN XY: 299534

African (AFR) AF: 0.861 AC: 10963 AN: 12736

American (AMR) AF: 0.889 AC: 20790 AN: 23392

Ashkenazi Jewish (ASJ) AF: 0.800 AC: 14033 AN: 17544

East Asian (EAS) AF: 0.792 AC: 23560 AN: 29746

South Asian (SAS) AF: 0.877 AC: 47953 AN: 54688

European-Finnish (FIN) AF: 0.808 AC: 37546 AN: 46486

Middle Eastern (MID) AF: 0.820 AC: 2921 AN: 3564

European-Non Finnish (NFE) AF: 0.801 AC: 269966 AN: 337056

Other (OTH) AF: 0.804 AC: 23564 AN: 29306

GnomAD4 genome AF: 0.830 AC: 126270 AN: 152068 Hom.: 52509 Cov.: 31 AF XY: 0.831 AC XY: 61760 AN XY: 74324

African (AFR) AF: 0.861 AC: 35733 AN: 41502

American (AMR) AF: 0.869 AC: 13249 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2786 AN: 3468

East Asian (EAS) AF: 0.768 AC: 3976 AN: 5176

South Asian (SAS) AF: 0.884 AC: 4266 AN: 4824

European-Finnish (FIN) AF: 0.810 AC: 8566 AN: 10574

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55043 AN: 67956

Other (OTH) AF: 0.817 AC: 1724 AN: 2110

Alfa AF: 0.788 Hom.: 2453

Bravo AF: 0.832

Asia WGS AF: 0.839 AC: 2907 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.12
DANN	Benign	0.15
PhyloP100		-0.39
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: rs2617169; hg19: chr12-10560824; COSMIC: COSV58672489; COSMIC: COSV58672489;