3-148697758-A-G

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

2

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)

Genome browser will be placed here

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
AGTR1NM_000685.5 linkc.-501A>G upstream_gene_variant ENST00000349243.8 NP_000676.1 P30556Q53YY0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AGTR1ENST00000349243.8 linkc.-501A>G upstream_gene_variant 1 NM_000685.5 ENSP00000273430.3 P30556
AGTR1ENST00000404754.2 linkc.-439A>G upstream_gene_variant 1 ENSP00000385612.2 P30556
AGTR1ENST00000497524.5 linkc.-417A>G upstream_gene_variant 1 ENSP00000419422.1 P30556
AGTR1ENST00000418473.7 linkc.-475A>G upstream_gene_variant 5 ENSP00000398832.4 P30556D3DNG8

Frequencies

GnomAD3 genomes
AF:
0.200
AC:
30433
AN:
152012
Hom.:
3299
Cov.:
32
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:
9
AN:
40
Hom.:
2
Cov.:
0
AF XY:
0.265
AC XY:
9
AN XY:
34
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AF:
0.500
AC:
1
AN:
2
Ashkenazi Jewish (ASJ)
AC:
0
AN:
0
East Asian (EAS)
AC:
0
AN:
0
South Asian (SAS)
AC:
0
AN:
0
European-Finnish (FIN)
AF:
0.125
AC:
1
AN:
8
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.208
AC:
5
AN:
24
Other (OTH)
AF:
0.333
AC:
2
AN:
6
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.565
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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.:
32
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:
86
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
0
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
0
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
16
DANN
Benign
0.65
PhyloP100
2.1
PromoterAI
0.027
Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs275653; hg19: chr3-148415545; API