rs2835872

Variant names:

• chr21-37654970-G-A
• rs2835872
• NM_002240.5:c.947-29486C>T

Variant summary

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

The NM_002240.5(KCNJ6):​c.947-29486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,032 control chromosomes in the GnomAD database, including 5,901 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 0.26 (5901 hom., cov: 31)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 12 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=-0.92).
• 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.947-29486C>T		intron_variant	Intron 3 of 3	ENST00000609713.2	NP_002231.1
KCNJ6-AS1	NR_183540.1	n.408-43585G>A		intron_variant	Intron 1 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000609713.2	c.947-29486C>T		intron_variant	Intron 3 of 3	1	NM_002240.5	ENSP00000477437.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40140 AN: 151912 Hom.: 5896 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.264 AC: 40166 AN: 152032 Hom.: 5901 Cov.: 31 AF XY: 0.267 AC XY: 19848 AN XY: 74304

African (AFR) AF: 0.143 AC: 5941 AN: 41468

American (AMR) AF: 0.289 AC: 4420 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3468

East Asian (EAS) AF: 0.125 AC: 647 AN: 5162

South Asian (SAS) AF: 0.309 AC: 1483 AN: 4804

European-Finnish (FIN) AF: 0.380 AC: 4021 AN: 10580

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21519 AN: 67958

Other (OTH) AF: 0.269 AC: 567 AN: 2106

Alfa AF: 0.299 Hom.: 31148

Bravo AF: 0.255

Asia WGS AF: 0.178 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.1
DANN	Benign	0.77
PhyloP100		0.12
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: rs2835872; hg19: chr21-39027272;