21-38259542-C-T

Position:

• chr21-38259542-C-T

Variant summary

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

The NM_170736.3(KCNJ15):​c.-117+2357C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 152,216 control chromosomes in the GnomAD database, including 45,095 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 0.76 (45095 hom., cov: 33)
• Consequence: KCNJ15 NM_170736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.13

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.-117+2357C>T		intron_variant		ENST00000398938.7	NP_733932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000398938.7	c.-117+2357C>T		intron_variant		1	NM_170736.3	ENSP00000381911.2

Frequencies

GnomAD3 genomes AF: 0.764 AC: 116233 AN: 152098 Hom.: 45042 Cov.: 33

Gnomad AFR AF: 0.890

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.614

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.639

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.720

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

GnomAD4 genome AF: 0.764 AC: 116333 AN: 152216 Hom.: 45095 Cov.: 33 AF XY: 0.756 AC XY: 56275 AN XY: 74414

Gnomad4 AFR AF: 0.890

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.703

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.714

Alfa AF: 0.752 Hom.: 18709

Bravo AF: 0.763

Asia WGS AF: 0.707 AC: 2460 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.059
DANN	Benign	0.62

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: rs2836249; hg19: chr21-39631464;