11-128912083-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000890.5(KCNJ5):c.810T>G(p.Leu270Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.824 in 1,613,502 control chromosomes in the GnomAD database, including 549,350 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. L270L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.84 ( 54355 hom., cov: 33)

Exomes 𝑓: 0.82 ( 494995 hom. )

Consequence

KCNJ5
NM_000890.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 1.91

Publications

34 publications found

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 Gene-Disease associations (from GenCC):

familial hyperaldosteronism type III
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)
Andersen-Tawil syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
long QT syndrome 13
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
long QT syndrome
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KCNJ5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 11-128912083-T-G is Benign according to our data. Variant chr11-128912083-T-G is described in ClinVar as Benign. ClinVar VariationId is 137991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.91 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000890.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KCNJ5	NM_000890.5	MANE Select	c.810T>G	p.Leu270Leu	synonymous	Exon 2 of 3	NP_000881.3
	KCNJ5	NM_001354169.2		c.810T>G	p.Leu270Leu	synonymous	Exon 3 of 4	NP_001341098.1	P48544

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KCNJ5	ENST00000529694.6	TSL:1 MANE Select	c.810T>G	p.Leu270Leu	synonymous	Exon 2 of 3	ENSP00000433295.1	P48544
KCNJ5	ENST00000338350.4	TSL:1	c.810T>G	p.Leu270Leu	synonymous	Exon 3 of 4	ENSP00000339960.4	P48544
KCNJ5	ENST00000533599.1	TSL:1	c.810T>G	p.Leu270Leu	synonymous	Exon 1 of 2	ENSP00000434266.1	P48544

Frequencies

GnomAD3 genomes

AF:

0.844

AC:

128333

AN:

152036

Hom.:

54311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.892

Gnomad AMI

AF:

0.865

Gnomad AMR

AF:

0.836

Gnomad ASJ

AF:

0.841

Gnomad EAS

AF:

0.879

Gnomad SAS

AF:

0.893

Gnomad FIN

AF:

0.795

Gnomad MID

AF:

0.826

Gnomad NFE

AF:

0.818

Gnomad OTH

AF:

0.857

GnomAD2 exomes

AF:

0.838

AC:

209044

AN:

249344

AF XY:

0.842

show subpopulations

Gnomad AFR exome

AF:

0.895

Gnomad AMR exome

AF:

0.814

Gnomad ASJ exome

AF:

0.848

Gnomad EAS exome

AF:

0.880

Gnomad FIN exome

AF:

0.793

Gnomad NFE exome

AF:

0.825

Gnomad OTH exome

AF:

0.836

GnomAD4 exome

AF:

0.822

AC:

1201864

AN:

1461348

Hom.:

494995

Cov.:

AF XY:

0.826

AC XY:

600315

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.899

AC:

30092

AN:

33472

American (AMR)

AF:

0.813

AC:

36349

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.847

AC:

22148

AN:

26134

East Asian (EAS)

AF:

0.872

AC:

34632

AN:

39700

South Asian (SAS)

AF:

0.890

AC:

76736

AN:

86258

European-Finnish (FIN)

AF:

0.789

AC:

41913

AN:

53112

Middle Eastern (MID)

AF:

0.885

AC:

5103

AN:

5764

European-Non Finnish (NFE)

AF:

0.814

AC:

904878

AN:

1111802

Other (OTH)

AF:

0.828

AC:

50013

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

12354

24707

37061

49414

61768

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20912

41824

62736

83648

104560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.844

AC:

128431

AN:

152154

Hom.:

54355

Cov.:

AF XY:

0.845

AC XY:

62859

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.892

AC:

37029

AN:

41514

American (AMR)

AF:

0.836

AC:

12786

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.841

AC:

2919

AN:

3470

East Asian (EAS)

AF:

0.879

AC:

4538

AN:

5160

South Asian (SAS)

AF:

0.893

AC:

4306

AN:

4824

European-Finnish (FIN)

AF:

0.795

AC:

8432

AN:

10602

Middle Eastern (MID)

AF:

0.823

AC:

242

AN:

294

European-Non Finnish (NFE)

AF:

0.818

AC:

55580

AN:

67972

Other (OTH)

AF:

0.856

AC:

1810

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1052

2104

3156

4208

5260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

892

1784

2676

3568

4460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.832

Hom.:

88646

Bravo

AF:

0.848

Asia WGS

AF:

0.883

AC:

3066

AN:

3476

EpiCase

AF:

0.833

EpiControl

AF:

0.833

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Familial hyperaldosteronism type III (2)

Cardiovascular phenotype (1)

Congenital long QT syndrome (1)

Long QT syndrome (1)

Long QT syndrome 13 (1)

Long QT syndrome 13;C3838758:Familial hyperaldosteronism type III (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.6

(source)

DANN

Benign

0.70

PhyloP100

1.9

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over