21-37965488-C-T

Variant names:

• chr21-37965488-C-T
• rs2836071
• ENST00000645093.1:c.-27-124779G>A

Variant summary

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

The ENST00000645093.1(KCNJ6):​c.-27-124779G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.089 in 152,226 control chromosomes in the GnomAD database, including 704 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 0.089 (704 hom., cov: 32)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 3 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]

DSCR4 (HGNC:3045): (Down syndrome critical region 4) The gene is found in a region of chromosome 21 that has been linked to the pathogenesis of Down syndrome. This gene is transcribed from a bi-directional promoter located in an endogenous retrovirus. [provided by RefSeq, Jan 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 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.-27-124779G>A		intron_variant	Intron 2 of 4			ENSP00000493772.1
DSCR4	ENST00000398948.5	n.315-12483G>A		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0890 AC: 13542 AN: 152108 Hom.: 704 Cov.: 32

Gnomad AFR AF: 0.0714

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0997

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0625

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.103

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

GnomAD4 genome AF: 0.0890 AC: 13550 AN: 152226 Hom.: 704 Cov.: 32 AF XY: 0.0905 AC XY: 6737 AN XY: 74432

African (AFR) AF: 0.0714 AC: 2966 AN: 41534

American (AMR) AF: 0.116 AC: 1778 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0997 AC: 346 AN: 3470

East Asian (EAS) AF: 0.236 AC: 1221 AN: 5166

South Asian (SAS) AF: 0.116 AC: 561 AN: 4818

European-Finnish (FIN) AF: 0.0625 AC: 662 AN: 10600

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0827 AC: 5625 AN: 68018

Other (OTH) AF: 0.102 AC: 215 AN: 2112

Alfa AF: 0.0863 Hom.: 1099

Bravo AF: 0.0915

Asia WGS AF: 0.140 AC: 487 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.11
DANN	Benign	0.48
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2836071; hg19: chr21-39337791;