chr21-38272924-G-C

Variant names:

• chr21-38272924-G-C
• rs743296
• NM_170736.3:c.-117+15739G>C

Variant summary

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

The NM_170736.3(KCNJ15):​c.-117+15739G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.798 in 152,168 control chromosomes in the GnomAD database, including 49,187 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 0.80 (49187 hom., cov: 33)
• Consequence: KCNJ15 NM_170736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0150
• Publications: 2 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.922 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.-117+15739G>C		intron	N/A	NP_733932.1
	KCNJ15	NM_001276435.2		c.-256+15739G>C		intron	N/A	NP_001263364.1
	KCNJ15	NM_001276436.2		c.-259+15739G>C		intron	N/A	NP_001263365.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.-117+15739G>C		intron	N/A	ENSP00000381911.2
	KCNJ15	ENST00000328656.8	TSL:1	c.-117+15739G>C		intron	N/A	ENSP00000331698.3
	KCNJ15	ENST00000398930.5	TSL:5	c.-220+367G>C		intron	N/A	ENSP00000381904.1

Frequencies

GnomAD3 genomes AF: 0.798 AC: 121372 AN: 152048 Hom.: 49125 Cov.: 33

Gnomad AFR AF: 0.929

Gnomad AMI AF: 0.612

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.712

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.748

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

GnomAD4 genome AF: 0.798 AC: 121487 AN: 152168 Hom.: 49187 Cov.: 33 AF XY: 0.793 AC XY: 58953 AN XY: 74370

African (AFR) AF: 0.930 AC: 38624 AN: 41552

American (AMR) AF: 0.638 AC: 9735 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2622 AN: 3468

East Asian (EAS) AF: 0.711 AC: 3673 AN: 5164

South Asian (SAS) AF: 0.747 AC: 3604 AN: 4824

European-Finnish (FIN) AF: 0.736 AC: 7772 AN: 10562

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.781 AC: 53117 AN: 68014

Other (OTH) AF: 0.748 AC: 1582 AN: 2114

Alfa AF: 0.732 Hom.: 2190

Bravo AF: 0.794

Asia WGS AF: 0.745 AC: 2591 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.7
DANN	Benign	0.47
PhyloP100		0.015
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs743296; hg19: chr21-39644846;