rs12721225

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000685.5(AGTR1):c.730G>T(p.Ala244Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00375 in 1,613,236 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0026 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0039 ( 31 hom. )

Consequence

AGTR1
NM_000685.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 6.86

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008590668).

BP6

Variant 3-148741765-G-T is Benign according to our data. Variant chr3-148741765-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 773450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0026 (395/152126) while in subpopulation SAS AF= 0.00875 (42/4798). AF 95% confidence interval is 0.00666. There are 1 homozygotes in gnomad4. There are 187 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5 link	c.730G>T	p.Ala244Ser	missense_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.730G>T	p.Ala244Ser	missense_variant	Exon 3 of 3	1	NM_000685.5	ENSP00000273430.3		P30556

Frequencies

GnomAD3 genomes

AF:

0.00261

AC:

396

AN:

152008

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000676

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00875

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00369

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00370

AC:

924

AN:

249984

Hom.:

AF XY:

0.00420

AC XY:

569

AN XY:

135394

show subpopulations

Gnomad AFR exome

AF:

0.000441

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00915

Gnomad FIN exome

AF:

0.000847

Gnomad NFE exome

AF:

0.00400

Gnomad OTH exome

AF:

0.00378

GnomAD4 exome

AF:

0.00387

AC:

5655

AN:

1461110

Hom.:

Cov.:

AF XY:

0.00417

AC XY:

3031

AN XY:

726882

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00948

Gnomad4 FIN exome

AF:

0.00106

Gnomad4 NFE exome

AF:

0.00371

Gnomad4 OTH exome

AF:

0.00407

GnomAD4 genome

AF:

0.00260

AC:

395

AN:

152126

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

187

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.000674

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00875

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.00369

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00413

Hom.:

Bravo

AF:

0.00251

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00156

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00512

AC:

ExAC

AF:

0.00402

AC:

488

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00528

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

AGTR1: BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Renal tubular dysgenesis

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

D;D;D;D;D;D;T;T

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

.;.;.;.;.;T;T;T

MetaRNN

Benign

0.0086

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

M;M;M;M;M;M;.;.

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

N;N;N;N;N;N;.;.

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D;D;D;D;D;.;.

Sift4G

Uncertain

0.028

D;D;D;D;D;D;D;D

Polyphen

0.99

D;D;D;D;D;D;.;.

Vest4

0.34

MVP

0.77

ClinPred

0.027

GERP RS

5.5

Varity_R

0.79

gMVP

0.41

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