21-38300702-C-G

Variant names:

• chr21-38300702-C-G
• rs9963
• NM_170736.3:c.*313C>G

Variant summary

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

The NM_170736.3(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 NM_170736.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.287
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.*313C>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7	c.*313C>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_170736.3	ENSP00000381911.2

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

African (AFR) AF: 0.879 AC: 2752 AN: 3132

American (AMR) AF: 0.675 AC: 3086 AN: 4570

Ashkenazi Jewish (ASJ) AF: 0.751 AC: 2676 AN: 3562

East Asian (EAS) AF: 0.727 AC: 4836 AN: 6648

South Asian (SAS) AF: 0.776 AC: 3813 AN: 4912

European-Finnish (FIN) AF: 0.759 AC: 14068 AN: 18546

Middle Eastern (MID) AF: 0.682 AC: 322 AN: 472

European-Non Finnish (NFE) AF: 0.797 AC: 48918 AN: 61376

Other (OTH) AF: 0.781 AC: 4975 AN: 6374

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

African (AFR) AF: 0.871 AC: 36182 AN: 41558

American (AMR) AF: 0.721 AC: 11023 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.747 AC: 2591 AN: 3468

East Asian (EAS) AF: 0.719 AC: 3729 AN: 5184

South Asian (SAS) AF: 0.767 AC: 3693 AN: 4814

European-Finnish (FIN) AF: 0.761 AC: 8070 AN: 10600

Middle Eastern (MID) AF: 0.684 AC: 201 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54149 AN: 68022

Other (OTH) AF: 0.757 AC: 1597 AN: 2110

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
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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: rs9963; hg19: chr21-39672624;