21-38305667-T-G

Variant names:

• chr21-38305667-T-G
• rs2836301
• NM_170736.3:c.*5278T>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.*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
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_170736.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	NM_170736.3	MANE Select	c.*5278T>G		3_prime_UTR	Exon 3 of 3	NP_733932.1
	KCNJ15	NM_001276435.2		c.*5278T>G		3_prime_UTR	Exon 5 of 5	NP_001263364.1
	KCNJ15	NM_001276436.2		c.*5278T>G		3_prime_UTR	Exon 5 of 5	NP_001263365.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.*5278T>G		3_prime_UTR	Exon 3 of 3	ENSP00000381911.2
	KCNJ15	ENST00000328656.8	TSL:1	c.*5278T>G		3_prime_UTR	Exon 4 of 4	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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.257 AC: 10674 AN: 41506

American (AMR) AF: 0.500 AC: 7638 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.536 AC: 1862 AN: 3472

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5178

South Asian (SAS) AF: 0.454 AC: 2195 AN: 4830

European-Finnish (FIN) AF: 0.511 AC: 5398 AN: 10568

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39997 AN: 67974

Other (OTH) AF: 0.461 AC: 972 AN: 2108

Alfa AF: 0.379 Hom.: 1213

Bravo AF: 0.453

Asia WGS AF: 0.352 AC: 1228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.0
DANN	Benign	0.67
PhyloP100		0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2836301; hg19: chr21-39677589;