rs2000457

Positions:

• chr21-38261523-T-A

Variant summary

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

The NM_170736.3(KCNJ15):​c.-117+4338T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,126 control chromosomes in the GnomAD database, including 11,395 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 0.35 (11395 hom., cov: 32)
• Consequence: KCNJ15 NM_170736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.-117+4338T>A		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+4338T>A		intron_variant		1	NM_170736.3	ENSP00000381911.2

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52607 AN: 152008 Hom.: 11398 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.346 AC: 52598 AN: 152126 Hom.: 11395 Cov.: 32 AF XY: 0.341 AC XY: 25388 AN XY: 74348

Gnomad4 AFR AF: 0.0998

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.442

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.437

Gnomad4 NFE AF: 0.500

Gnomad4 OTH AF: 0.341

Alfa AF: 0.418 Hom.: 1865

Bravo AF: 0.326

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.24
DANN	Benign	0.79

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: rs2000457; hg19: chr21-39633445;