Variant 11-128917535-G-T 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_000890.5(KCNJ5):c.*804G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 152,168 control chromosomes in the GnomAD database, including 41,963 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 41963 hom., cov: 34)

Exomes 𝑓: 0.72 ( 46 hom. )

Failed GnomAD Quality Control

Consequence

KCNJ5
NM_000890.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.163

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-128917535-G-T is Benign according to our data. Variant chr11-128917535-G-T is described in ClinVar as [Benign]. Clinvar id is 303649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
KCNJ5	NM_000890.5 linkuse as main transcript	c.*804G>T	3_prime_UTR_variant	3/3	ENST00000529694.6
KCNJ5	NM_001354169.2 linkuse as main transcript	c.*804G>T	3_prime_UTR_variant	4/4
KCNJ5	XM_011542810.4 linkuse as main transcript	c.*804G>T	3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KCNJ5	ENST00000529694.6 linkuse as main transcript	c.*804G>T		3_prime_UTR_variant	3/3	1	NM_000890.5	P1

Frequencies

GnomAD3 genomes

AF:

0.741

AC:

112674

AN:

152050

Hom.:

41932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.784

Gnomad AMI

AF:

0.793

Gnomad AMR

AF:

0.740

Gnomad ASJ

AF:

0.755

Gnomad EAS

AF:

0.669

Gnomad SAS

AF:

0.771

Gnomad FIN

AF:

0.681

Gnomad MID

AF:

0.753

Gnomad NFE

AF:

0.725

Gnomad OTH

AF:

0.773

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.719

AC:

128

AN:

178

Hom.:

Cov.:

AF XY:

0.714

AC XY:

AN XY:

126

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 AMR exome

AF:

1.00

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.500

Gnomad4 FIN exome

AF:

0.750

Gnomad4 NFE exome

AF:

0.713

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.741

AC:

112764

AN:

152168

Hom.:

41963

Cov.:

AF XY:

0.741

AC XY:

55138

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.784

Gnomad4 AMR

AF:

0.740

Gnomad4 ASJ

AF:

0.755

Gnomad4 EAS

AF:

0.669

Gnomad4 SAS

AF:

0.770

Gnomad4 FIN

AF:

0.681

Gnomad4 NFE

AF:

0.725

Gnomad4 OTH

AF:

0.774

Alfa

AF:

0.714

Hom.:

6307

Bravo

AF:

0.745

Asia WGS

AF:

0.746

AC:

2588

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Familial hyperaldosteronism type III

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Congenital long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

1.4

DANN

Benign

0.76

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