NM_170736.3:c.-117+4338T>A

Variant names:

• chr21-38261523-T-A
• rs2000457
• NM_170736.3:c.-117+4338T>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+4338T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,126 control chromosomes in the GnomAD database, including 11,395 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 0.35 (11395 hom., cov: 32)
• Consequence: KCNJ15 NM_170736.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.32
• 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 = 0.496 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+4338T>A		intron	N/A	NP_733932.1
	KCNJ15	NM_001276435.2		c.-256+4338T>A		intron	N/A	NP_001263364.1
	KCNJ15	NM_001276436.2		c.-259+4338T>A		intron	N/A	NP_001263365.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ15	ENST00000398938.7	TSL:1 MANE Select	c.-117+4338T>A		intron	N/A	ENSP00000381911.2
	KCNJ15	ENST00000328656.8	TSL:1	c.-117+4338T>A		intron	N/A	ENSP00000331698.3
	KCNJ15	ENST00000612702.4	TSL:4	c.-256+4338T>A		intron	N/A	ENSP00000484960.1

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52607 AN: 152008 Hom.: 11398 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.324

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.442

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.437

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.346 AC: 52598 AN: 152126 Hom.: 11395 Cov.: 32 AF XY: 0.341 AC XY: 25388 AN XY: 74348

African (AFR) AF: 0.0998 AC: 4143 AN: 41532

American (AMR) AF: 0.297 AC: 4534 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.442 AC: 1533 AN: 3472

East Asian (EAS) AF: 0.230 AC: 1192 AN: 5176

South Asian (SAS) AF: 0.302 AC: 1456 AN: 4826

European-Finnish (FIN) AF: 0.437 AC: 4612 AN: 10554

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 34009 AN: 67962

Other (OTH) AF: 0.341 AC: 720 AN: 2112

Alfa AF: 0.418 Hom.: 1865

Bravo AF: 0.326

Asia WGS AF: 0.235 AC: 816 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	0.24
DANN	Benign	0.79
PhyloP100		-1.3
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: rs2000457; hg19: chr21-39633445;