rs928769

Positions:

• chr21-38265507-G-A
• chr21-38265507-G-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+8322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,132 control chromosomes in the GnomAD database, including 12,559 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 0.38 (12559 hom., cov: 33)
• Consequence: KCNJ15 NM_170736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.655

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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.-117+8322G>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+8322G>A		intron_variant		1	NM_170736.3	ENSP00000381911	P1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57682 AN: 152014 Hom.: 12537 Cov.: 33

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.339

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

GnomAD4 genome AF: 0.380 AC: 57753 AN: 152132 Hom.: 12559 Cov.: 33 AF XY: 0.381 AC XY: 28359 AN XY: 74392

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.271

Gnomad4 OTH AF: 0.336

Alfa AF: 0.310 Hom.: 4908

Bravo AF: 0.383

Asia WGS AF: 0.462 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.4
DANN	Benign	0.85

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: rs928769; hg19: chr21-39637429;