chr21-38234847-C-T

Variant names:

• chr21-38234847-C-T
• rs2186344
• NM_001276437.2:c.-199+4824C>T

Variant summary

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

The NM_001276437.2(KCNJ15):​c.-199+4824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,000 control chromosomes in the GnomAD database, including 17,005 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 (17005 hom., cov: 33)
• Consequence: KCNJ15 NM_001276437.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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]

ENSG00000289927 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.838 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.-199+4824C>T		intron	N/A	NP_001263366.1
	KCNJ15	NM_001276438.2		c.-117+4824C>T		intron	N/A	NP_001263367.1
	KCNJ15	NM_001276439.2		c.-257+4824C>T		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.-398-22199C>T		intron	N/A	ENSP00000447111.1
	KCNJ15	ENST00000547595.5	TSL:2	c.-116-62079C>T		intron	N/A	ENSP00000450254.1
	KCNJ15	ENST00000548700.5	TSL:3	c.-107-62079C>T		intron	N/A	ENSP00000448886.1

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70123 AN: 151882 Hom.: 16976 Cov.: 33

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.502

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.462 AC: 70185 AN: 152000 Hom.: 17005 Cov.: 33 AF XY: 0.475 AC XY: 35273 AN XY: 74290

African (AFR) AF: 0.388 AC: 16077 AN: 41428

American (AMR) AF: 0.502 AC: 7676 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1756 AN: 3470

East Asian (EAS) AF: 0.859 AC: 4453 AN: 5186

South Asian (SAS) AF: 0.603 AC: 2907 AN: 4824

European-Finnish (FIN) AF: 0.601 AC: 6337 AN: 10548

Middle Eastern (MID) AF: 0.579 AC: 169 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29198 AN: 67954

Other (OTH) AF: 0.499 AC: 1049 AN: 2104

Alfa AF: 0.427 Hom.: 10069

Bravo AF: 0.451

Asia WGS AF: 0.699 AC: 2431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.21
DANN	Benign	0.49
PhyloP100		-1.5

Splicing

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

Other links and lift over

dbSNP: rs2186344; hg19: chr21-39606769;