rs2835872

chr21-37654970-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.947-29486C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,032 control chromosomes in the GnomAD database, including 5,901 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 0.26 (5901 hom., cov: 31)
• Consequence: KCNJ6 NM_002240.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ6	NM_002240.5	c.947-29486C>T		intron_variant		ENST00000609713.2
KCNJ6-AS1	NR_183540.1	n.408-43585G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ6	ENST00000609713.2	c.947-29486C>T		intron_variant		1	NM_002240.5	P1
	ENST00000667151.1	n.238-4224G>A		intron_variant, non_coding_transcript_variant
KCNJ6	ENST00000645093.1	c.947-29486C>T		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40140 AN: 151912 Hom.: 5896 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.268

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

GnomAD4 genome AF: 0.264 AC: 40166 AN: 152032 Hom.: 5901 Cov.: 31 AF XY: 0.267 AC XY: 19848 AN XY: 74304

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.289

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.380

Gnomad4 NFE AF: 0.317

Gnomad4 OTH AF: 0.269

Alfa AF: 0.308 Hom.: 14912

Bravo AF: 0.255

Asia WGS AF: 0.178 AC: 623 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	5.1
Dann	Benign	0.77

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: rs2835872; hg19: chr21-39027272;