21-38305667-T-G

Position:

• chr21-38305667-T-G

Variant summary

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

The NM_170736.3(KCNJ15):​c.*5278T>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 0.465 in 152,122 control chromosomes in the GnomAD database, including 18,082 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 0.46 (18082 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: KCNJ15 NM_170736.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.903

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 = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_170736.3	c.*5278T>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.*5278T>G		3_prime_UTR_variant	3/3	1	NM_170736.3	ENSP00000381911.2
KCNJ15	ENST00000328656.8	c.*5278T>G		3_prime_UTR_variant	4/4	1		ENSP00000331698.3

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70676 AN: 152004 Hom.: 18084 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.536

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.511

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.464

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.465 AC: 70687 AN: 152122 Hom.: 18082 Cov.: 33 AF XY: 0.461 AC XY: 34317 AN XY: 74382

Gnomad4 AFR AF: 0.257

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.536

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.511

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.461

Alfa AF: 0.388 Hom.: 1188

Bravo AF: 0.453

Asia WGS AF: 0.352 AC: 1228 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	3.0
DANN	Benign	0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2836301; hg19: chr21-39677589;