chr11-128911465-C-T

Position:

chr11-128911465-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000890.5(KCNJ5):c.192C>T(p.His64=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 1,614,258 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00020 ( 2 hom. )

Consequence

KCNJ5
NM_000890.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.864

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 11-128911465-C-T is Benign according to our data. Variant chr11-128911465-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 378008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-128911465-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.864 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00167 (254/152374) while in subpopulation AFR AF= 0.0057 (237/41590). AF 95% confidence interval is 0.0051. There are 3 homozygotes in gnomad4. There are 122 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 254 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KCNJ5	NM_000890.5 linkuse as main transcript	c.192C>T	p.His64=	synonymous_variant	2/3	ENST00000529694.6	NP_000881.3
KCNJ5	NM_001354169.2 linkuse as main transcript	c.192C>T	p.His64=	synonymous_variant	3/4		NP_001341098.1
KCNJ5	XM_011542810.4 linkuse as main transcript	c.192C>T	p.His64=	synonymous_variant	2/3		XP_011541112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
KCNJ5	ENST00000529694.6 linkuse as main transcript	c.192C>T	p.His64=	synonymous_variant	2/3	1	NM_000890.5	ENSP00000433295	P1
KCNJ5	ENST00000338350.4 linkuse as main transcript	c.192C>T	p.His64=	synonymous_variant	3/4	1		ENSP00000339960	P1
KCNJ5	ENST00000533599.1 linkuse as main transcript	c.192C>T	p.His64=	synonymous_variant	1/2	1		ENSP00000434266	P1

Frequencies

GnomAD3 genomes

AF:

0.00167

AC:

255

AN:

152256

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00574

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00105

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000493

AC:

124

AN:

251442

Hom.:

AF XY:

0.000449

AC XY:

AN XY:

135902

show subpopulations

Gnomad AFR exome

AF:

0.00640

Gnomad AMR exome

AF:

0.000491

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000204

AC:

298

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000190

AC XY:

138

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00681

Gnomad4 AMR exome

AF:

0.000537

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000198

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00167

AC:

254

AN:

152374

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00570

Gnomad4 AMR

AF:

0.00105

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000965

Hom.:

Bravo

AF:

0.00190

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 05, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Long QT syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 19, 2024

- -

Cardiovascular phenotype

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 04, 2018

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

3.7

DANN

Benign

0.70

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