12-10392998-A-T

Variant names:

• chr12-10392998-A-T
• rs2617160
• ENST00000539300.5:n.*75+812T>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+812T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,072 control chromosomes in the GnomAD database, including 32,240 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 0.65 (32240 hom., cov: 32)
• Consequence: KLRC4-KLRK1 ENST00000539300.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 16 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000539300.5. 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
	KLRC4-KLRK1	NM_001199805.1		c.-123+812T>A		intron	N/A	NP_001186734.1
	KLRK1-AS1	NR_120430.1		n.503-3181A>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC4-KLRK1	ENST00000539300.5	TSL:2	n.*75+812T>A		intron	N/A	ENSP00000455951.1
	KLRK1-AS1	ENST00000500682.1	TSL:2	n.503-3181A>T		intron	N/A
	KLRC4-KLRK1	ENST00000539370.5	TSL:2	n.469-4123T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98368 AN: 151952 Hom.: 32216 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.600

Gnomad EAS AF: 0.558

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.638

Gnomad NFE AF: 0.706

Gnomad OTH AF: 0.638

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

GnomAD4 genome AF: 0.647 AC: 98443 AN: 152072 Hom.: 32240 Cov.: 32 AF XY: 0.645 AC XY: 47948 AN XY: 74322

African (AFR) AF: 0.553 AC: 22922 AN: 41464

American (AMR) AF: 0.688 AC: 10508 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.600 AC: 2081 AN: 3470

East Asian (EAS) AF: 0.558 AC: 2890 AN: 5176

South Asian (SAS) AF: 0.555 AC: 2675 AN: 4820

European-Finnish (FIN) AF: 0.685 AC: 7242 AN: 10570

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.706 AC: 47993 AN: 67982

Other (OTH) AF: 0.641 AC: 1352 AN: 2110

Alfa AF: 0.577 Hom.: 1715

Bravo AF: 0.642

Asia WGS AF: 0.575 AC: 2004 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.25
DANN	Benign	0.33
PhyloP100		-1.2

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: rs2617160; hg19: chr12-10545597;