rs7275707

Variant names:

• chr21-37916637-A-G
• rs7275707
• ENST00000645093.1:c.-27-75928T>C

Your query was ambiguous. Multiple possible variants found:

• chr21-37916637-A-G
• chr21-37916637-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000645093.1(KCNJ6):​c.-27-75928T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 151,864 control chromosomes in the GnomAD database, including 36,496 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 0.68 (36496 hom., cov: 31)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30
• Publications: 6 publications found

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]

KCNJ6 Gene-Disease associations (from GenCC):

• Keppen-Lubinsky syndrome

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000645093.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	NM_002240.5	MANE Select	c.-781T>C		upstream_gene	N/A	NP_002231.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000645093.1		c.-27-75928T>C		intron	N/A	ENSP00000493772.1
	KCNJ6	ENST00000609713.2	TSL:1 MANE Select	c.-781T>C		upstream_gene	N/A	ENSP00000477437.1

Frequencies

GnomAD3 genomes AF: 0.683 AC: 103665 AN: 151748 Hom.: 36463 Cov.: 31

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.696

Gnomad SAS AF: 0.742

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.666

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

GnomAD4 genome AF: 0.683 AC: 103753 AN: 151864 Hom.: 36496 Cov.: 31 AF XY: 0.683 AC XY: 50700 AN XY: 74188

African (AFR) AF: 0.855 AC: 35486 AN: 41502

American (AMR) AF: 0.692 AC: 10562 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2119 AN: 3468

East Asian (EAS) AF: 0.696 AC: 3553 AN: 5106

South Asian (SAS) AF: 0.741 AC: 3572 AN: 4822

European-Finnish (FIN) AF: 0.611 AC: 6436 AN: 10538

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39898 AN: 67840

Other (OTH) AF: 0.669 AC: 1415 AN: 2114

Alfa AF: 0.619 Hom.: 53402

Bravo AF: 0.698

Asia WGS AF: 0.706 AC: 2454 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.33
PhyloP100		-2.3
PromoterAI		-0.0070	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7275707; hg19: chr21-39288940;