1-230714126-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000679738.1(AGT):n.-71G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,032 control chromosomes in the GnomAD database, including 28,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 28493 hom., cov: 31)

Exomes 𝑓: 0.48 ( 23 hom. )

Consequence

AGT
ENST00000679738.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -1.48

Publications

241 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:

ENSG00000244137 (HGNC:58238):

ENSG00000244137 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-230714126-C-T is Benign according to our data. Variant chr1-230714126-C-T is described in ClinVar as Benign. ClinVar VariationId is 296090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3 link	c.-30-3273G>A		intron_variant	Intron 1 of 4		NP_001369746.2
AGT	NM_001384479.1 link	c.-71G>A		upstream_gene_variant		ENST00000366667.6	NP_001371408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6 link	c.-71G>A		upstream_gene_variant		1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes

AF:

0.583

AC:

88384

AN:

151728

Hom.:

28429

Cov.:

show subpopulations

Gnomad AFR

AF:

0.842

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.640

Gnomad ASJ

AF:

0.448

Gnomad EAS

AF:

0.831

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.443

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.562

GnomAD4 exome

AF:

0.478

AC:

AN:

186

Hom.:

Cov.:

AF XY:

0.481

AC XY:

AN XY:

154

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.750

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.443

AC:

AN:

158

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.535

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.583

AC:

88505

AN:

151846

Hom.:

28493

Cov.:

AF XY:

0.587

AC XY:

43579

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.843

AC:

34955

AN:

41472

American (AMR)

AF:

0.641

AC:

9783

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.448

AC:

1556

AN:

3470

East Asian (EAS)

AF:

0.831

AC:

4259

AN:

5128

South Asian (SAS)

AF:

0.622

AC:

2980

AN:

4788

European-Finnish (FIN)

AF:

0.443

AC:

4661

AN:

10514

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28577

AN:

67884

Other (OTH)

AF:

0.566

AC:

1197

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

1631

3262

4893

6524

8155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

720

1440

2160

2880

3600

<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:

0.488

Hom.:

54099

Bravo

AF:

0.610

Asia WGS

AF:

0.728

AC:

2530

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Renal tubular dysgenesis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertension, essential, susceptibility to

Benign:1

Dec 24, 2010

OMIM

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Renal tubular dysgenesis of genetic origin

Benign:1

Apr 24, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.75

(source)

DANN

Benign

0.60

PhyloP100

-1.5

PromoterAI

-0.087

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

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