chr21-37921561-T-C

Variant names:

• chr21-37921561-T-C
• rs9983444
• ENST00000645093.1:c.-27-80852A>G

Variant summary

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

The ENST00000645093.1(KCNJ6):​c.-27-80852A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,260 control chromosomes in the GnomAD database, including 2,299 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 0.15 (2299 hom., cov: 32)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KCNJ6	ENST00000645093.1	c.-27-80852A>G		intron_variant	Intron 2 of 4			ENSP00000493772.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23558 AN: 152142 Hom.: 2300 Cov.: 32

Gnomad AFR AF: 0.0453

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.182

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.155 AC: 23557 AN: 152260 Hom.: 2299 Cov.: 32 AF XY: 0.154 AC XY: 11452 AN XY: 74440

African (AFR) AF: 0.0452 AC: 1880 AN: 41564

American (AMR) AF: 0.140 AC: 2138 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 633 AN: 3472

East Asian (EAS) AF: 0.0811 AC: 421 AN: 5188

South Asian (SAS) AF: 0.115 AC: 553 AN: 4826

European-Finnish (FIN) AF: 0.190 AC: 2010 AN: 10602

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.224 AC: 15234 AN: 67994

Other (OTH) AF: 0.165 AC: 350 AN: 2116

Alfa AF: 0.168 Hom.: 401

Bravo AF: 0.146

Asia WGS AF: 0.114 AC: 396 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	1.2
DANN	Benign	0.50
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs9983444; hg19: chr21-39293864;