Genetic Variant AGTR1:c.-501A>G (chr3-148697758-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000685.5(AGTR1):c.-501A>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,170 control chromosomes in the GnomAD database, including 3,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3310 hom., cov: 32)

Exomes 𝑓: 0.23 ( 2 hom. )

Consequence

AGTR1
NM_000685.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.07

Publications

31 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5 link	c.-501A>G		upstream_gene_variant		ENST00000349243.8	NP_000676.1	P30556Q53YY0

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AGTR1	ENST00000349243.8 link	c.-501A>G	upstream_gene_variant	1	NM_000685.5	ENSP00000273430.3	P30556
AGTR1	ENST00000404754.2 link	c.-439A>G	upstream_gene_variant	1		ENSP00000385612.2	P30556
AGTR1	ENST00000497524.5 link	c.-417A>G	upstream_gene_variant	1		ENSP00000419422.1	P30556
AGTR1	ENST00000418473.7 link	c.-475A>G	upstream_gene_variant	5		ENSP00000398832.4	P30556D3DNG8

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30433

AN:

152012

Hom.:

3299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.258

Gnomad AMI

AF:

0.257

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.102

Gnomad SAS

AF:

0.185

Gnomad FIN

AF:

0.148

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.186

Gnomad OTH

AF:

0.216

GnomAD4 exome

AF:

0.225

AC:

AN:

Hom.:

Cov.:

AF XY:

0.265

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.208

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.565

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:

0.200

AC:

30468

AN:

152130

Hom.:

3310

Cov.:

AF XY:

0.198

AC XY:

14730

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.258

AC:

10709

AN:

41518

American (AMR)

AF:

0.154

AC:

2354

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

992

AN:

3470

East Asian (EAS)

AF:

0.103

AC:

530

AN:

5164

South Asian (SAS)

AF:

0.183

AC:

883

AN:

4822

European-Finnish (FIN)

AF:

0.148

AC:

1569

AN:

10594

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.186

AC:

12660

AN:

67954

Other (OTH)

AF:

0.214

AC:

451

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1249

2498

3747

4996

6245

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

326

652

978

1304

1630

<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:

0.127

Hom.:

252

Bravo

AF:

0.201

Asia WGS

AF:

0.146

AC:

513

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

2.1

PromoterAI

0.027

Neutral

(source)

Splicing

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

Computational scores

Splicing

Publications

Other links and lift over