rs2836055

Positions:

• chr21-37925512-T-C

Variant summary

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

The ENST00000645093.1(KCNJ6):​c.-27-84803A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,200 control chromosomes in the GnomAD database, including 5,474 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 0.20 (5474 hom., cov: 32)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.284

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.37925512T>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000645093.1	c.-27-84803A>G		intron_variant				ENSP00000493772.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30938 AN: 152082 Hom.: 5464 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0768

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.203 AC: 30972 AN: 152200 Hom.: 5474 Cov.: 32 AF XY: 0.194 AC XY: 14454 AN XY: 74434

Gnomad4 AFR AF: 0.489

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.0760

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.174

Alfa AF: 0.143 Hom.: 1413

Bravo AF: 0.222

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.77

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2836055; hg19: chr21-39297815;