rs3825295

Positions:

• chr12-10410076-A-G
• chr12-10410076-A-T

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

KLRC4-KLRK1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
KLRC4-KLRK1	NM_001199805.1	c.-488+23T>C		intron_variant			NP_001186734.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0214

Gnomad4 EAS AF: 0.261

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.0701

Gnomad4 NFE AF: 0.00876

Gnomad4 OTH AF: 0.0766

Alfa AF: 0.0426 Hom.: 49

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3825295; hg19: chr12-10562675;