rs9963

Positions:

• chr21-38300702-C-G
• chr21-38300702-C-T
• chr21-38300702-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000398938.7(KCNJ15):​c.*313C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 261,834 control chromosomes in the GnomAD database, including 82,414 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 0.80 (48944 hom., cov: 33)
  • Exomes 𝑓: 0.78 (33470 hom.)
• Consequence: KCNJ15 ENST00000398938.7 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287

Genes affected

KCNJ15 (HGNC:6261): (potassium inwardly rectifying channel subfamily J member 15) Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Eight transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Feb 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.*313C>G		3_prime_UTR_variant	3/3	ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7	c.*313C>G		3_prime_UTR_variant	3/3	1	NM_170736.3	ENSP00000381911	P1

Frequencies

GnomAD3 genomes AF: 0.800 AC: 121711 AN: 152122 Hom.: 48913 Cov.: 33

Gnomad AFR AF: 0.871

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.747

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.761

Gnomad MID AF: 0.678

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.780 AC: 85446 AN: 109592 Hom.: 33470 Cov.: 1 AF XY: 0.781 AC XY: 43319 AN XY: 55452

Gnomad4 AFR exome AF: 0.879

Gnomad4 AMR exome AF: 0.675

Gnomad4 ASJ exome AF: 0.751

Gnomad4 EAS exome AF: 0.727

Gnomad4 SAS exome AF: 0.776

Gnomad4 FIN exome AF: 0.759

Gnomad4 NFE exome AF: 0.797

Gnomad4 OTH exome AF: 0.781

GnomAD4 genome AF: 0.800 AC: 121790 AN: 152242 Hom.: 48944 Cov.: 33 AF XY: 0.797 AC XY: 59326 AN XY: 74440

Gnomad4 AFR AF: 0.871

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.747

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.767

Gnomad4 FIN AF: 0.761

Gnomad4 NFE AF: 0.796

Gnomad4 OTH AF: 0.757

Alfa AF: 0.758 Hom.: 2300

Bravo AF: 0.796

Asia WGS AF: 0.733 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	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

Publications

LitVar

Other links and lift over

dbSNP: rs9963; hg19: chr21-39672624;