rs5183

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_000685.5(AGTR1):c.1062A>G(p.Pro354Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0673 in 1,613,898 control chromosomes in the GnomAD database, including 6,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1976 hom., cov: 32)

Exomes 𝑓: 0.062 ( 4131 hom. )

Consequence

AGTR1
NM_000685.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.24

Publications

24 publications found

Variant links:

Genes affected

AGTR1 (HGNC:336): (angiotensin II receptor type 1) Angiotensin II is a potent vasopressor hormone and a primary regulator of aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. It acts through at least two types of receptors. This gene encodes the type 1 receptor which is thought to mediate the major cardiovascular effects of angiotensin II. This gene may play a role in the generation of reperfusion arrhythmias following restoration of blood flow to ischemic or infarcted myocardium. It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2020]

AGTR1 Gene-Disease associations (from GenCC):

renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
essential hypertension, genetic
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

AGTR1 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=-0.99).

BP6

Variant 3-148742097-A-G is Benign according to our data. Variant chr3-148742097-A-G is described in ClinVar as Benign. ClinVar VariationId is 256758.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.24 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5 link	c.1062A>G	p.Pro354Pro	synonymous_variant	Exon 3 of 3	ENST00000349243.8	NP_000676.1	P30556Q53YY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8 link	c.1062A>G	p.Pro354Pro	synonymous_variant	Exon 3 of 3	1	NM_000685.5	ENSP00000273430.3		P30556

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18214

AN:

151938

Hom.:

1965

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.0670

Gnomad AMR

AF:

0.0552

Gnomad ASJ

AF:

0.0302

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0449

Gnomad FIN

AF:

0.0784

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0566

Gnomad OTH

AF:

0.0883

GnomAD2 exomes

AF:

0.0615

AC:

15377

AN:

249974

AF XY:

0.0586

show subpopulations

Gnomad AFR exome

AF:

0.301

Gnomad AMR exome

AF:

0.0341

Gnomad ASJ exome

AF:

0.0258

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0694

Gnomad NFE exome

AF:

0.0540

Gnomad OTH exome

AF:

0.0510

GnomAD4 exome

AF:

0.0618

AC:

90319

AN:

1461842

Hom.:

4131

Cov.:

AF XY:

0.0605

AC XY:

43998

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.301

AC:

10072

AN:

33478

American (AMR)

AF:

0.0360

AC:

1610

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0275

AC:

718

AN:

26132

East Asian (EAS)

AF:

0.000176

AC:

AN:

39696

South Asian (SAS)

AF:

0.0462

AC:

3985

AN:

86258

European-Finnish (FIN)

AF:

0.0700

AC:

3740

AN:

53410

Middle Eastern (MID)

AF:

0.0562

AC:

324

AN:

5768

European-Non Finnish (NFE)

AF:

0.0592

AC:

65784

AN:

1111984

Other (OTH)

AF:

0.0675

AC:

4079

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

5048

10096

15144

20192

25240

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2594

5188

7782

10376

12970

<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:

0.120

AC:

18258

AN:

152056

Hom.:

1976

Cov.:

AF XY:

0.118

AC XY:

8747

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.293

AC:

12155

AN:

41420

American (AMR)

AF:

0.0550

AC:

841

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0302

AC:

105

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.0439

AC:

211

AN:

4808

European-Finnish (FIN)

AF:

0.0784

AC:

831

AN:

10594

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0566

AC:

3851

AN:

67994

Other (OTH)

AF:

0.0874

AC:

185

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

719

1438

2157

2876

3595

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

360

540

720

900

<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:

0.0716

Hom.:

2092

Bravo

AF:

0.128

Asia WGS

AF:

0.0310

AC:

106

AN:

3478

EpiCase

AF:

0.0569

EpiControl

AF:

0.0573

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 10, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Renal tubular dysgenesis

Benign:1

Jan 12, 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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.011

(source)

DANN

Benign

0.30

PhyloP100

-1.2

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