rs2154553

chr21-37632199-G-Achr21-37632199-G-Tchr21-37632199-G-C

Variant summary

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

The NM_002240.5(KCNJ6):c.947-6715C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 149,722 control chromosomes in the GnomAD database, including 37,803 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 0.71 (37803 hom., cov: 28)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5	c.947-6715C>T		intron_variant		ENST00000609713.2
KCNJ6-AS1	NR_183540.1	n.408-66356G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000609713.2	c.947-6715C>T		intron_variant		1	NM_002240.5	P1
	ENST00000667151.1	n.161-14348G>A		intron_variant, non_coding_transcript_variant
KCNJ6	ENST00000645093.1	c.947-6715C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 105885 AN: 149606 Hom.: 37781 Cov.: 28

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.498

Gnomad AMR AF: 0.763

Gnomad ASJ AF: 0.688

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.672

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.704

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

GnomAD4 genome AF: 0.708 AC: 105956 AN: 149722 Hom.: 37803 Cov.: 28 AF XY: 0.706 AC XY: 51552 AN XY: 73012

Gnomad4 AFR AF: 0.731

Gnomad4 AMR AF: 0.763

Gnomad4 ASJ AF: 0.688

Gnomad4 EAS AF: 0.825

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.703

Alfa AF: 0.694 Hom.: 34252

Bravo AF: 0.717

Asia WGS AF: 0.772 AC: 2680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.71

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: rs2154553; hg19: chr21-39004501;