12-10393326-C-T

Variant names:

• chr12-10393326-C-T
• rs2733840
• ENST00000539300.5:n.*75+484G>A

Variant summary

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

The ENST00000539300.5(KLRC4-KLRK1):​n.*75+484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.83 in 152,210 control chromosomes in the GnomAD database, including 52,499 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 (52499 hom., cov: 33)
• Consequence: KLRC4-KLRK1 ENST00000539300.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.335
• Publications: 6 publications found

Genes affected

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]

KLRK1-AS1 (HGNC:54868): (KLRK1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.861 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC4-KLRK1	NM_001199805.1	c.-123+484G>A		intron_variant	Intron 5 of 12		NP_001186734.1
KLRK1-AS1	NR_120430.1	n.503-2853C>T		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC4-KLRK1	ENST00000539300.5	n.*75+484G>A		intron_variant	Intron 5 of 12	2		ENSP00000455951.1

Frequencies

GnomAD3 genomes AF: 0.830 AC: 126195 AN: 152092 Hom.: 52441 Cov.: 33

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.767

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.811

Gnomad MID AF: 0.829

Gnomad NFE AF: 0.809

Gnomad OTH AF: 0.816

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.830 AC: 126315 AN: 152210 Hom.: 52499 Cov.: 33 AF XY: 0.830 AC XY: 61784 AN XY: 74404

African (AFR) AF: 0.862 AC: 35784 AN: 41504

American (AMR) AF: 0.868 AC: 13270 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2764 AN: 3472

East Asian (EAS) AF: 0.768 AC: 3974 AN: 5176

South Asian (SAS) AF: 0.883 AC: 4269 AN: 4832

European-Finnish (FIN) AF: 0.811 AC: 8580 AN: 10586

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

European-Non Finnish (NFE) AF: 0.809 AC: 55015 AN: 68026

Other (OTH) AF: 0.818 AC: 1731 AN: 2116

Alfa AF: 0.822 Hom.: 28895

Bravo AF: 0.832

Asia WGS AF: 0.837 AC: 2905 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.37
PhyloP100		-0.34

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: rs2733840; hg19: chr12-10545925;