NM_002240.5:c.947-34691T>C

Variant names:

• chr21-37660175-A-G
• rs2835880
• NM_002240.5:c.947-34691T>C

Variant summary

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

The NM_002240.5(KCNJ6):​c.947-34691T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,134 control chromosomes in the GnomAD database, including 6,756 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 0.29 (6756 hom., cov: 33)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 1 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]

ENSG00000286717 (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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KCNJ6	NM_002240.5	c.947-34691T>C		intron_variant	Intron 3 of 3	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.408-38380A>G		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.947-34691T>C		intron_variant	Intron 3 of 3	1	NM_002240.5	ENSP00000477437.1
ENSG00000286717	ENST00000667151.1	n.1219A>G		non_coding_transcript_exon_variant	Exon 3 of 3
KCNJ6	ENST00000645093.1	c.947-34691T>C		intron_variant	Intron 4 of 4			ENSP00000493772.1
KCNJ6-AS1	ENST00000838485.1	n.86+15163A>G		intron_variant	Intron 1 of 5

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44507 AN: 152016 Hom.: 6752 Cov.: 33

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.502

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.319

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.381

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.293 AC: 44542 AN: 152134 Hom.: 6756 Cov.: 33 AF XY: 0.294 AC XY: 21874 AN XY: 74372

African (AFR) AF: 0.239 AC: 9911 AN: 41514

American (AMR) AF: 0.302 AC: 4608 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.319 AC: 1106 AN: 3470

East Asian (EAS) AF: 0.135 AC: 696 AN: 5162

South Asian (SAS) AF: 0.309 AC: 1492 AN: 4826

European-Finnish (FIN) AF: 0.381 AC: 4031 AN: 10590

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21538 AN: 67978

Other (OTH) AF: 0.293 AC: 619 AN: 2110

Alfa AF: 0.308 Hom.: 919

Bravo AF: 0.288

Asia WGS AF: 0.185 AC: 650 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.85
PhyloP100		-0.013
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2835880; hg19: chr21-39032477;