chr21-37668040-C-T

Variant names:

• chr21-37668040-C-T
• rs2835886
• NM_002240.5:c.947-42556G>A

Variant summary

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

The NM_002240.5(KCNJ6):​c.947-42556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.479 in 151,696 control chromosomes in the GnomAD database, including 18,190 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 0.48 (18190 hom., cov: 33)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 3 publications found

Genes affected

KCNJ6 (HGNC:6267): (potassium inwardly rectifying channel subfamily J member 6) This gene encodes a member of the G protein-coupled inwardly-rectifying potassium channel family of inward rectifier potassium channels. This type of potassium channel allows a greater flow of potassium into the cell than out of it. These proteins modulate many physiological processes, including heart rate in cardiac cells and circuit activity in neuronal cells, through G-protein coupled receptor stimulation. Mutations in this gene are associated with Keppen-Lubinsky Syndrome, a rare condition characterized by severe developmental delay, facial dysmorphism, and intellectual disability. [provided by RefSeq, Apr 2015]

KCNJ6-AS1 (HGNC:):

KCNJ6-AS1 (HGNC:41352): (KCNJ6 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002240.5. 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
	KCNJ6	NM_002240.5	MANE Select	c.947-42556G>A		intron	N/A	NP_002231.1
	KCNJ6-AS1	NR_183540.1		n.408-30515C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.947-42556G>A		intron	N/A	ENSP00000477437.1
	KCNJ6	ENST00000645093.1		c.947-42556G>A		intron	N/A	ENSP00000493772.1
	KCNJ6-AS1	ENST00000838485.1		n.86+23028C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72641 AN: 151578 Hom.: 18183 Cov.: 33

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.479 AC: 72684 AN: 151696 Hom.: 18190 Cov.: 33 AF XY: 0.478 AC XY: 35456 AN XY: 74102

African (AFR) AF: 0.642 AC: 26505 AN: 41280

American (AMR) AF: 0.465 AC: 7099 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1597 AN: 3460

East Asian (EAS) AF: 0.419 AC: 2150 AN: 5128

South Asian (SAS) AF: 0.492 AC: 2375 AN: 4826

European-Finnish (FIN) AF: 0.362 AC: 3812 AN: 10542

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27671 AN: 67878

Other (OTH) AF: 0.475 AC: 1002 AN: 2108

Alfa AF: 0.430 Hom.: 60115

Bravo AF: 0.490

Asia WGS AF: 0.489 AC: 1697 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.16
DANN	Benign	0.69
PhyloP100		-2.0
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: rs2835886; hg19: chr21-39040342; COSMIC: COSV55721919;