21-37945114-A-G

Variant names:

• chr21-37945114-A-G
• rs7275197
• ENST00000645093.1:c.-27-104405T>C

Variant summary

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

The ENST00000645093.1(KCNJ6):​c.-27-104405T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 152,088 control chromosomes in the GnomAD database, including 2,917 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 0.19 (2917 hom., cov: 31)
• Consequence: KCNJ6 ENST00000645093.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.770
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.285 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.-27-104405T>C		intron_variant	Intron 2 of 4			ENSP00000493772.1

Frequencies

GnomAD3 genomes AF: 0.187 AC: 28351 AN: 151968 Hom.: 2918 Cov.: 31

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.187 AC: 28379 AN: 152088 Hom.: 2917 Cov.: 31 AF XY: 0.188 AC XY: 14005 AN XY: 74346

African (AFR) AF: 0.104 AC: 4308 AN: 41512

American (AMR) AF: 0.165 AC: 2528 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3470

East Asian (EAS) AF: 0.297 AC: 1526 AN: 5138

South Asian (SAS) AF: 0.154 AC: 745 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2441 AN: 10574

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.229 AC: 15548 AN: 67968

Other (OTH) AF: 0.184 AC: 389 AN: 2112

Alfa AF: 0.217 Hom.: 6090

Bravo AF: 0.177

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.69
PhyloP100		0.77

Splicing

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

Other links and lift over

dbSNP: rs7275197; hg19: chr21-39317417;