21-37917643-C-T

Variant names:

• chr21-37917643-C-T
• rs6517442
• ENST00000645093.1:c.-27-76934G>A

Variant summary

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

The ENST00000645093.1(KCNJ6):​c.-27-76934G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,212 control chromosomes in the GnomAD database, including 44,437 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 0.76 (44437 hom., cov: 32)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 17 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.897 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ6	ENST00000645093.1		c.-27-76934G>A		intron	N/A	ENSP00000493772.1	P48051

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115194 AN: 152092 Hom.: 44402 Cov.: 32

Gnomad AFR AF: 0.905

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.690

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.747

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

GnomAD4 genome AF: 0.757 AC: 115287 AN: 152212 Hom.: 44437 Cov.: 32 AF XY: 0.758 AC XY: 56396 AN XY: 74402

African (AFR) AF: 0.905 AC: 37583 AN: 41550

American (AMR) AF: 0.768 AC: 11745 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.734 AC: 2547 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3588 AN: 5164

South Asian (SAS) AF: 0.816 AC: 3934 AN: 4820

European-Finnish (FIN) AF: 0.715 AC: 7579 AN: 10604

Middle Eastern (MID) AF: 0.687 AC: 202 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45904 AN: 67986

Other (OTH) AF: 0.749 AC: 1582 AN: 2112

Alfa AF: 0.715 Hom.: 27236

Bravo AF: 0.769

Asia WGS AF: 0.746 AC: 2592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.59
DANN	Benign	0.24
PhyloP100		-0.64

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6517442;

hg19: chr21-39289946;