21-38256530-C-G

Variant names:

• chr21-38256530-C-G
• rs13433471
• NM_001276437.2:c.-198-574C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001276437.2(KCNJ15):​c.-198-574C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,174 control chromosomes in the GnomAD database, including 2,126 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 0.15 (2126 hom., cov: 29)
• Consequence: KCNJ15 NM_001276437.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.635
• Publications: 0 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 (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001276437.2. 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_001276437.2		c.-198-574C>G		intron	N/A	NP_001263366.1
	KCNJ15	NM_001276438.2		c.-117+26507C>G		intron	N/A	NP_001263367.1
	KCNJ15	NM_001276439.2		c.-256-516C>G		intron	N/A	NP_001263368.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000547341.5	TSL:3	c.-398-516C>G		intron	N/A	ENSP00000447111.1
	KCNJ15	ENST00000547595.5	TSL:2	c.-116-40396C>G		intron	N/A	ENSP00000450254.1
	KCNJ15	ENST00000548700.5	TSL:3	c.-107-40396C>G		intron	N/A	ENSP00000448886.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22064 AN: 151058 Hom.: 2119 Cov.: 29

Gnomad AFR AF: 0.0431

Gnomad AMI AF: 0.0978

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.400

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.225

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.146 AC: 22081 AN: 151174 Hom.: 2126 Cov.: 29 AF XY: 0.153 AC XY: 11300 AN XY: 73858

African (AFR) AF: 0.0431 AC: 1771 AN: 41100

American (AMR) AF: 0.181 AC: 2759 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3466

East Asian (EAS) AF: 0.399 AC: 2040 AN: 5108

South Asian (SAS) AF: 0.288 AC: 1379 AN: 4782

European-Finnish (FIN) AF: 0.225 AC: 2348 AN: 10414

Middle Eastern (MID) AF: 0.170 AC: 49 AN: 288

European-Non Finnish (NFE) AF: 0.160 AC: 10828 AN: 67784

Other (OTH) AF: 0.134 AC: 281 AN: 2098

Alfa AF: 0.0886 Hom.: 130

Bravo AF: 0.137

Asia WGS AF: 0.336 AC: 1170 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.86
DANN	Benign	0.54
PhyloP100		-0.64
PromoterAI		-0.018	Neutral

Splicing

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

Other links and lift over

dbSNP: rs13433471; hg19: chr21-39628452;