Variant summary

Our verdict is Benign. The variant received -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 (★★). Synonymous variant affecting the same amino acid position (i.e. A244A) has been classified 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:5

Conservation

PhyloP100: 6.86

Publications

19 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 -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 31 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000685.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGTR1	NM_000685.5	MANE Select	c.730G>T	p.Ala244Ser	missense	Exon 3 of 3	NP_000676.1
AGTR1	NM_001382736.1		c.730G>T	p.Ala244Ser	missense	Exon 2 of 2	NP_001369665.1
AGTR1	NM_001382737.1		c.730G>T	p.Ala244Ser	missense	Exon 3 of 3	NP_001369666.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.730G>T	p.Ala244Ser	missense	Exon 3 of 3	ENSP00000273430.3
AGTR1	ENST00000404754.2	TSL:1	c.730G>T	p.Ala244Ser	missense	Exon 2 of 2	ENSP00000385612.2
AGTR1	ENST00000497524.5	TSL:1	c.730G>T	p.Ala244Ser	missense	Exon 2 of 2	ENSP00000419422.1

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

GnomAD2 exomes

AF:

0.00370

AC:

924

AN:

249984

AF XY:

0.00420

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 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

African (AFR)

AF:

0.000388

AC:

AN:

33478

American (AMR)

AF:

0.000872

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0121

AC:

315

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00948

AC:

818

AN:

86252

European-Finnish (FIN)

AF:

0.00106

AC:

AN:

52794

Middle Eastern (MID)

AF:

0.00676

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00371

AC:

4129

AN:

1111894

Other (OTH)

AF:

0.00407

AC:

246

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

333

666

998

1331

1664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

156

312

468

624

780

<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:

0.00260

AC:

395

AN:

152126

Hom.:

Cov.:

AF XY:

0.00252

AC XY:

187

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.000674

AC:

AN:

41524

American (AMR)

AF:

0.000785

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00875

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.000378

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00369

AC:

251

AN:

67990

Other (OTH)

AF:

0.00332

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00372

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

ClinVar submissions as Germline

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Renal tubular dysgenesis (1)

Renal tubular dysgenesis of genetic origin (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.62

Eigen

Pathogenic

0.82

Eigen_PC

Pathogenic

0.80

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

PhyloP100

6.9

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.20

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.028

Polyphen

0.99

Vest4

0.34

MVP

0.77

ClinPred

0.027

GERP RS

5.5

Varity_R

0.79

gMVP

0.41

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs12721225

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over