rs11702683

chr21-37916461-T-Cchr21-37916461-T-Gchr21-37916461-T-A

Variant summary

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

The ENST00000645093.1(KCNJ6):c.-27-75752A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 149,386 control chromosomes in the GnomAD database, including 40,399 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 0.73 (40379 hom., cov: 27)
  • Exomes 𝑓: 0.51 (20 hom.)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.71

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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5			upstream_gene_variant		ENST00000609713.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000645093.1	c.-27-75752A>G		intron_variant				P1
KCNJ6	ENST00000609713.2			upstream_gene_variant		1	NM_002240.5	P1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 108340 AN: 149128 Hom.: 40325 Cov.: 27

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.589

Gnomad AMR AF: 0.747

Gnomad ASJ AF: 0.660

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.809

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.710

GnomAD4 exome AF: 0.507 AC: 69 AN: 136 Hom.: 20 Cov.: 0 AF XY: 0.451 AC XY: 37 AN XY: 82

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.508

GnomAD4 genome AF: 0.727 AC: 108456 AN: 149250 Hom.: 40379 Cov.: 27 AF XY: 0.730 AC XY: 53086 AN XY: 72686

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.747

Gnomad4 ASJ AF: 0.660

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.713

Alfa AF: 0.555 Hom.: 1538

Bravo AF: 0.734

Asia WGS AF: 0.837 AC: 2910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
Cadd	Benign	16
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11702683; hg19: chr21-39288764;