chr1-230705941-T-C

Variant names:

Variant summary

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

The NM_001384479.1(AGT):c.1089A>G(p.Leu363Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 1,614,020 control chromosomes in the GnomAD database, including 695,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.95 ( 68411 hom., cov: 31)

Exomes 𝑓: 0.93 ( 627123 hom. )

Consequence

AGT
NM_001384479.1 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.681

Publications

22 publications found

Variant links:

Genes affected

AGT (HGNC:333): (angiotensinogen) The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

AGT Gene-Disease associations (from GenCC):

renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

AGT 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=-0.89).

BP6

Variant 1-230705941-T-C is Benign according to our data. Variant chr1-230705941-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.681 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1 link	c.1089A>G	p.Leu363Leu	synonymous_variant	Exon 3 of 5	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3 link	c.1089A>G	p.Leu363Leu	synonymous_variant	Exon 3 of 5		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6 link	c.1089A>G	p.Leu363Leu	synonymous_variant	Exon 3 of 5	1	NM_001384479.1	ENSP00000355627.5		P01019

Frequencies

GnomAD3 genomes

AF:

0.947

AC:

144113

AN:

152118

Hom.:

68355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.985

Gnomad AMI

AF:

0.977

Gnomad AMR

AF:

0.949

Gnomad ASJ

AF:

0.946

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.984

Gnomad FIN

AF:

0.950

Gnomad MID

AF:

0.940

Gnomad NFE

AF:

0.917

Gnomad OTH

AF:

0.940

GnomAD2 exomes

AF:

0.945

AC:

237033

AN:

250920

AF XY:

0.944

show subpopulations

Gnomad AFR exome

AF:

0.986

Gnomad AMR exome

AF:

0.966

Gnomad ASJ exome

AF:

0.943

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.942

Gnomad NFE exome

AF:

0.914

Gnomad OTH exome

AF:

0.940

GnomAD4 exome

AF:

0.926

AC:

1353575

AN:

1461784

Hom.:

627123

Cov.:

AF XY:

0.927

AC XY:

674465

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.987

AC:

33036

AN:

33480

American (AMR)

AF:

0.966

AC:

43197

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.943

AC:

24647

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39697

AN:

39700

South Asian (SAS)

AF:

0.981

AC:

84568

AN:

86242

European-Finnish (FIN)

AF:

0.942

AC:

50301

AN:

53416

Middle Eastern (MID)

AF:

0.960

AC:

5538

AN:

5768

European-Non Finnish (NFE)

AF:

0.914

AC:

1016208

AN:

1111924

Other (OTH)

AF:

0.934

AC:

56383

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

6029

12057

18086

24114

30143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21520

43040

64560

86080

107600

<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:

0.947

AC:

144228

AN:

152236

Hom.:

68411

Cov.:

AF XY:

0.950

AC XY:

70692

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.985

AC:

40935

AN:

41564

American (AMR)

AF:

0.949

AC:

14518

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.946

AC:

3286

AN:

3472

East Asian (EAS)

AF:

1.00

AC:

5144

AN:

5146

South Asian (SAS)

AF:

0.984

AC:

4749

AN:

4826

European-Finnish (FIN)

AF:

0.950

AC:

10079

AN:

10606

Middle Eastern (MID)

AF:

0.932

AC:

274

AN:

294

European-Non Finnish (NFE)

AF:

0.917

AC:

62368

AN:

68006

Other (OTH)

AF:

0.940

AC:

1984

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

382

764

1146

1528

1910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

910

1820

2730

3640

4550

<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:

0.929

Hom.:

79118

Bravo

AF:

0.949

Asia WGS

AF:

0.991

AC:

3445

AN:

3478

EpiCase

AF:

0.918

EpiControl

AF:

0.917

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Renal tubular dysgenesis

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Renal tubular dysgenesis of genetic origin;CN305331:Essential hypertension, genetic

Benign:1

Nov 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

(source)

DANN

Benign

0.58

PhyloP100

-0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over