rs7275197

chr21-37945114-A-G

Variant summary

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

The ENST00000645093.1(KCNJ6):c.-27-104405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,088 control chromosomes in the GnomAD database, including 2,917 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 0.19 (2917 hom., cov: 31)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000645093.1	c.-27-104405T>C		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28351 AN: 151968 Hom.: 2918 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.187 AC: 28379 AN: 152088 Hom.: 2917 Cov.: 31 AF XY: 0.188 AC XY: 14005 AN XY: 74346

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.297

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.184

Alfa AF: 0.222 Hom.: 4937

Bravo AF: 0.177

Asia WGS AF: 0.242 AC: 841 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	13
Dann	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7275197; hg19: chr21-39317417;