chr21-38256487-A-G

Position:

• chr21-38256487-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001276437.2(KCNJ15):​c.-198-617A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 151,392 control chromosomes in the GnomAD database, including 2,312 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 0.10 (2312 hom., cov: 29)
• Consequence: KCNJ15 NM_001276437.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.06

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ15	NM_001276437.2	c.-198-617A>G		intron_variant			NP_001263366.1
KCNJ15	NM_001276438.2	c.-117+26464A>G		intron_variant			NP_001263367.1
KCNJ15	NM_001276439.2	c.-256-559A>G		intron_variant			NP_001263368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ15	ENST00000547341.5	c.-398-559A>G		intron_variant		3		ENSP00000447111
KCNJ15	ENST00000547595.5	c.-116-40439A>G		intron_variant		2		ENSP00000450254
KCNJ15	ENST00000548700.5	c.-107-40439A>G		intron_variant		3		ENSP00000448886

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15868 AN: 151290 Hom.: 2307 Cov.: 29

Gnomad AFR AF: 0.325

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0426

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.00990

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0203

Gnomad OTH AF: 0.0820

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

GnomAD4 genome AF: 0.105 AC: 15894 AN: 151392 Hom.: 2312 Cov.: 29 AF XY: 0.0997 AC XY: 7374 AN XY: 73986

Gnomad4 AFR AF: 0.325

Gnomad4 AMR AF: 0.0424

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.000775

Gnomad4 SAS AF: 0.0472

Gnomad4 FIN AF: 0.00990

Gnomad4 NFE AF: 0.0202

Gnomad4 OTH AF: 0.0813

Alfa AF: 0.0550 Hom.: 207

Bravo AF: 0.115

Asia WGS AF: 0.0570 AC: 197 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.012
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2836247; hg19: chr21-39628409;