rs3825295

Variant names:

• chr12-10410076-A-G
• rs3825295
• NM_001199805.1:c.-488+23T>C

Your query was ambiguous. Multiple possible variants found:

• chr12-10410076-A-G
• chr12-10410076-A-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.-488+23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.102 in 99,908 control chromosomes in the GnomAD database, including 715 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 0.10 (714 hom., cov: 28)
  • Exomes 𝑓: 0.039 (1 hom.)
• Consequence: KLRC4-KLRK1 NM_001199805.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC4-KLRK1	NM_001199805.1	c.-488+23T>C		intron_variant	Intron 1 of 12		NP_001186734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC4-KLRK1	ENST00000543812.5	n.-63+23T>C		intron_variant	Intron 1 of 12	2		ENSP00000457500.1
KLRC4-KLRK1	ENST00000585507.5	n.-63+23T>C		intron_variant	Intron 1 of 10	5		ENSP00000465434.1
KLRC4-KLRK1	ENST00000588263.5	n.-153+23T>C		intron_variant	Intron 1 of 10	5		ENSP00000468074.1

Frequencies

GnomAD3 genomes AF: 0.102 AC: 10177 AN: 99680 Hom.: 712 Cov.: 28

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00190

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0214

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.0481

Gnomad NFE AF: 0.00870

Gnomad OTH AF: 0.0747

GnomAD4 exome AF: 0.0391 AC: 5 AN: 128 Hom.: 1 Cov.: 0 AF XY: 0.0465 AC XY: 4 AN XY: 86

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.167 AC: 1 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 108

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.102 AC: 10194 AN: 99780 Hom.: 714 Cov.: 28 AF XY: 0.111 AC XY: 5393 AN XY: 48780

African (AFR) AF: 0.143 AC: 5436 AN: 37948

American (AMR) AF: 0.187 AC: 1640 AN: 8758

Ashkenazi Jewish (ASJ) AF: 0.0214 AC: 47 AN: 2194

East Asian (EAS) AF: 0.261 AC: 928 AN: 3550

South Asian (SAS) AF: 0.389 AC: 1295 AN: 3330

European-Finnish (FIN) AF: 0.0701 AC: 420 AN: 5988

Middle Eastern (MID) AF: 0.0469 AC: 9 AN: 192

European-Non Finnish (NFE) AF: 0.00876 AC: 315 AN: 35950

Other (OTH) AF: 0.0766 AC: 103 AN: 1344

Alfa AF: 0.102 Hom.: 673

Bravo AF: 0.0730

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.9
DANN	Benign	0.30
PhyloP100		0.51
PromoterAI		-0.0047	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3825295; hg19: chr12-10562675;