Variant chr11-128891433-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000890.5(KCNJ5):c.-299C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.14 ( 811 hom., cov: 16)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ5
NM_000890.5 5_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.635

Variant links:

Genes affected

KCNJ5 (HGNC:6266): (potassium inwardly rectifying channel subfamily J member 5) This gene encodes an integral membrane protein which belongs to one of seven subfamilies of inward-rectifier potassium channel proteins called potassium channel subfamily J. The encoded protein is a subunit of the potassium channel which is homotetrameric. It is controlled by G-proteins and has a greater tendency to allow potassium to flow into a cell rather than out of a cell. Naturally occurring mutations in this gene are associated with aldosterone-producing adenomas. [provided by RefSeq, Aug 2017]

KCNJ5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.21).

BP6

Variant 11-128891433-C-G is Benign according to our data. Variant chr11-128891433-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 878222.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KCNJ5	NM_000890.5 linkuse as main transcript	c.-299C>G		5_prime_UTR_variant	1/3	ENST00000529694.6
KCNJ5	NM_001354169.2 linkuse as main transcript	c.-388C>G		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ5	ENST00000529694.6 linkuse as main transcript	c.-299C>G		5_prime_UTR_variant	1/3	1	NM_000890.5	P1
KCNJ5	ENST00000338350.4 linkuse as main transcript			upstream_gene_variant		1		P1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

10928

AN:

80922

Hom.:

807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.221

Gnomad AMI

AF:

0.247

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.224

Gnomad EAS

AF:

0.123

Gnomad SAS

AF:

0.0583

Gnomad FIN

AF:

0.0454

Gnomad MID

AF:

0.0864

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.151

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

480

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

368

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.135

AC:

10934

AN:

80966

Hom.:

811

Cov.:

AF XY:

0.128

AC XY:

4967

AN XY:

38726

show subpopulations

Gnomad4 AFR

AF:

0.221

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.224

Gnomad4 EAS

AF:

0.122

Gnomad4 SAS

AF:

0.0583

Gnomad4 FIN

AF:

0.0454

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.150

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Familial hyperaldosteronism type III

Uncertain:1

Uncertain significance, 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.2

CADD

Benign

4.1

DANN

Benign

0.40

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