NM_170736.3:c.-117+8322G>A

Variant names:

• chr21-38265507-G-A
• rs928769
• NM_170736.3:c.-117+8322G>A

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+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
• Publications: 12 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	NM_170736.3	MANE Select	c.-117+8322G>A		intron	N/A	NP_733932.1	Q99712
	KCNJ15	NM_001276435.2		c.-256+8322G>A		intron	N/A	NP_001263364.1	Q99712
	KCNJ15	NM_001276436.2		c.-259+8322G>A		intron	N/A	NP_001263365.1	Q99712

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.-117+8322G>A		intron	N/A	ENSP00000381911.2	Q99712
	KCNJ15	ENST00000328656.8	TSL:1	c.-117+8322G>A		intron	N/A	ENSP00000331698.3	Q99712
	KCNJ15	ENST00000612702.4	TSL:4	c.-256+8322G>A		intron	N/A	ENSP00000484960.1	Q99712

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

African (AFR) AF: 0.596 AC: 24713 AN: 41480

American (AMR) AF: 0.311 AC: 4764 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.280 AC: 972 AN: 3470

East Asian (EAS) AF: 0.442 AC: 2282 AN: 5168

South Asian (SAS) AF: 0.416 AC: 2005 AN: 4822

European-Finnish (FIN) AF: 0.341 AC: 3606 AN: 10586

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18445 AN: 67988

Other (OTH) AF: 0.336 AC: 708 AN: 2110

Alfa AF: 0.310 Hom.: 6496

Bravo AF: 0.383

Asia WGS AF: 0.462 AC: 1610 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	3.4
DANN	Benign	0.85
PhyloP100		0.66
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: rs928769; hg19: chr21-39637429;