rs728010

Variant names:

• chr12-10400668-G-A
• rs728010
• ENST00000539300.5:n.*18-6801C>T

Variant summary

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

The NM_001199805.1(KLRC4-KLRK1):​c.-180-6801C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,742 control chromosomes in the GnomAD database, including 2,925 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 0.18 (2925 hom., cov: 31)
• Consequence: KLRC4-KLRK1 NM_001199805.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365
• Publications: 7 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199805.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC4-KLRK1	NM_001199805.1		c.-180-6801C>T		intron	N/A	NP_001186734.1	P26718-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC4-KLRK1	ENST00000539300.5	TSL:2	n.*18-6801C>T		intron	N/A	ENSP00000455951.1	H3BQV0
	KLRC4-KLRK1	ENST00000539370.5	TSL:2	n.468+6968C>T		intron	N/A
	KLRC4-KLRK1	ENST00000543572.6	TSL:2	n.*17+6968C>T		intron	N/A	ENSP00000456286.1	H3BRK7

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27829 AN: 151624 Hom.: 2921 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.209

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.184 AC: 27856 AN: 151742 Hom.: 2925 Cov.: 31 AF XY: 0.187 AC XY: 13887 AN XY: 74132

African (AFR) AF: 0.264 AC: 10933 AN: 41378

American (AMR) AF: 0.183 AC: 2790 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1084 AN: 5166

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4816

European-Finnish (FIN) AF: 0.163 AC: 1714 AN: 10534

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8494 AN: 67860

Other (OTH) AF: 0.175 AC: 368 AN: 2102

Alfa AF: 0.159 Hom.: 1346

Bravo AF: 0.187

Asia WGS AF: 0.263 AC: 911 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	6.1
DANN	Benign	0.59
PhyloP100		-0.36

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs728010;

hg19: chr12-10553267;