Variant rs1053074 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_002241.5(KCNJ10):c.*2062T>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 0.456 in 151,462 control chromosomes in the GnomAD database, including 16,696 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16616 hom., cov: 28)

Exomes 𝑓: 0.36 ( 80 hom. )

Consequence

KCNJ10
NM_002241.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.67

Variant links:

Genes affected

KCNJ10 (HGNC:6256): (potassium inwardly rectifying channel subfamily J member 10) This gene encodes a member of the inward rectifier-type potassium channel family, characterized by having a greater tendency to allow potassium to flow into, rather than out of, a cell. The encoded protein may form a heterodimer with another potassium channel protein and may be responsible for the potassium buffering action of glial cells in the brain. Mutations in this gene have been associated with seizure susceptibility of common idiopathic generalized epilepsy syndromes. [provided by RefSeq, Jul 2008]

KCNJ10 links:

KCNJ10 (HGNC:):

KCNJ10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 1-160039331-A-C is Benign according to our data. Variant chr1-160039331-A-C is described in ClinVar as [Benign]. Clinvar id is 293090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.607 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KCNJ10	NM_002241.5 linkuse as main transcript	c.*2062T>G		3_prime_UTR_variant	2/2	ENST00000644903.1	NP_002232.2	P78508

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KCNJ10	ENST00000644903 linkuse as main transcript	c.*2062T>G		3_prime_UTR_variant	2/2		NM_002241.5	ENSP00000495557.1		P78508

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

68675

AN:

150496

Hom.:

16600

Cov.:

show subpopulations

Gnomad AFR

AF:

0.613

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.443

Gnomad ASJ

AF:

0.384

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.469

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.398

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.365

AC:

310

AN:

850

Hom.:

Cov.:

AF XY:

0.355

AC XY:

210

AN XY:

592

show subpopulations

Gnomad4 AFR exome

AF:

0.667

Gnomad4 AMR exome

AF:

0.250

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0500

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.367

Gnomad4 OTH exome

AF:

0.500

GnomAD4 genome

AF:

0.456

AC:

68736

AN:

150612

Hom.:

16616

Cov.:

AF XY:

0.452

AC XY:

33245

AN XY:

73510

show subpopulations

Gnomad4 AFR

AF:

0.613

Gnomad4 AMR

AF:

0.442

Gnomad4 ASJ

AF:

0.384

Gnomad4 EAS

AF:

0.335

Gnomad4 SAS

AF:

0.470

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.398

Gnomad4 OTH

AF:

0.418

Alfa

AF:

0.410

Hom.:

17611

Bravo

AF:

0.467

Asia WGS

AF:

0.394

AC:

1363

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Autosomal recessive nonsyndromic hearing loss 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

EAST syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.8

DANN

Benign

0.68

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