Variant 21-37625125-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002240.5(KCNJ6):c.*34C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00829 in 1,398,072 control chromosomes in the GnomAD database, including 215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 70 hom., cov: 33)

Exomes 𝑓: 0.0069 ( 145 hom. )

Consequence

KCNJ6
NM_002240.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.146

Variant links:

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 links:

ENSG00000286717 (HGNC:):

ENSG00000286717 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 21-37625125-G-C is Benign according to our data. Variant chr21-37625125-G-C is described in ClinVar as [Benign]. Clinvar id is 1245230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ6	NM_002240.5 linkuse as main transcript	c.*34C>G		3_prime_UTR_variant	4/4	ENST00000609713.2	NP_002231.1	P48051
KCNJ6-AS1	NR_183540.1 linkuse as main transcript	n.408-73430G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KCNJ6	ENST00000609713.2 linkuse as main transcript	c.*34C>G	3_prime_UTR_variant	4/4	1	NM_002240.5	ENSP00000477437.1	P48051
KCNJ6	ENST00000645093.1 linkuse as main transcript	c.*34C>G	3_prime_UTR_variant	5/5			ENSP00000493772.1	P48051
ENSG00000286717	ENST00000667151.1 linkuse as main transcript	n.161-21422G>C	intron_variant

Frequencies

GnomAD3 genomes

AF:

0.0199

AC:

3032

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0499

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.0681

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.0196

GnomAD3 exomes

AF:

0.0155

AC:

3586

AN:

231442

Hom.:

AF XY:

0.0142

AC XY:

1778

AN XY:

125156

show subpopulations

Gnomad AFR exome

AF:

0.0502

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.0156

Gnomad EAS exome

AF:

0.0690

Gnomad SAS exome

AF:

0.0196

Gnomad FIN exome

AF:

0.000453

Gnomad NFE exome

AF:

0.00228

Gnomad OTH exome

AF:

0.0100

GnomAD4 exome

AF:

0.00686

AC:

8540

AN:

1245762

Hom.:

145

Cov.:

AF XY:

0.00703

AC XY:

4409

AN XY:

626792

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.0194

Gnomad4 ASJ exome

AF:

0.0157

Gnomad4 EAS exome

AF:

0.0526

Gnomad4 SAS exome

AF:

0.0194

Gnomad4 FIN exome

AF:

0.000623

Gnomad4 NFE exome

AF:

0.00186

Gnomad4 OTH exome

AF:

0.0115

GnomAD4 genome

AF:

0.0200

AC:

3045

AN:

152310

Hom.:

Cov.:

AF XY:

0.0194

AC XY:

1446

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0499

Gnomad4 AMR

AF:

0.0191

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.0681

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.0241

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.0231

Asia WGS

AF:

0.0590

AC:

204

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 20, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.42

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over