rs2836048

chr21-37911995-G-A

Variant summary

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

The NM_002240.5(KCNJ6):c.-28+3889C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,958 control chromosomes in the GnomAD database, including 16,038 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 0.41 (16038 hom., cov: 32)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.712 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5	c.-28+3889C>T		intron_variant		ENST00000609713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000609713.2	c.-28+3889C>T		intron_variant		1	NM_002240.5	P1
KCNJ6	ENST00000645093.1	c.-27-71286C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61691 AN: 151840 Hom.: 15992 Cov.: 32

Gnomad AFR AF: 0.719

Gnomad AMI AF: 0.258

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.407 AC: 61791 AN: 151958 Hom.: 16038 Cov.: 32 AF XY: 0.406 AC XY: 30174 AN XY: 74256

Gnomad4 AFR AF: 0.719

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.427

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.360

Alfa AF: 0.270 Hom.: 13594

Bravo AF: 0.434

Asia WGS AF: 0.551 AC: 1908 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	3.2
Dann	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs2836048; hg19: chr21-39284298;