GeneBe

chr3-148697697-A-C

Variant names:

Variant summary

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

The NM_000685.5(AGTR1):​c.-562A>C 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 152,068 control chromosomes in the GnomAD database, including 3,275 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 ( 3275 hom., cov: 32)
Exomes 𝑓: 0.083 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

AGTR1
NM_000685.5 upstream_gene

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0720

Publications

12 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
  • essential hypertension, genetic
    Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

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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 = 0.253 is higher than 0.05.

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

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGTR1
NM_000685.5
MANE Select
c.-562A>C
upstream_gene
N/ANP_000676.1P30556
AGTR1
NM_001382736.1
c.-500A>C
upstream_gene
N/ANP_001369665.1Q53YY0
AGTR1
NM_001382737.1
c.-584A>C
upstream_gene
N/ANP_001369666.1P30556

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
AGTR1
ENST00000349243.8
TSL:1 MANE Select
c.-562A>C
upstream_gene
N/AENSP00000273430.3P30556
AGTR1
ENST00000404754.2
TSL:1
c.-500A>C
upstream_gene
N/AENSP00000385612.2P30556
AGTR1
ENST00000497524.5
TSL:1
c.-478A>C
upstream_gene
N/AENSP00000419422.1P30556

Frequencies

GnomAD3 genomes
AF:
0.200
AC:
30373
AN:
151952
Hom.:
3264
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.257
Gnomad AMI
AF:
0.257
Gnomad AMR
AF:
0.154
Gnomad ASJ
AF:
0.285
Gnomad EAS
AF:
0.103
Gnomad SAS
AF:
0.185
Gnomad FIN
AF:
0.147
Gnomad MID
AF:
0.283
Gnomad NFE
AF:
0.186
Gnomad OTH
AF:
0.216
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0833
AC:
1
AN:
12
Hom.:
0
AF XY:
0.100
AC XY:
1
AN XY:
10
show subpopulations
African (AFR)
AC:
0
AN:
0
American (AMR)
AC:
0
AN:
0
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:
0.00
AC:
0
AN:
6
Middle Eastern (MID)
AC:
0
AN:
0
European-Non Finnish (NFE)
AF:
0.167
AC:
1
AN:
6
Other (OTH)
AC:
0
AN:
0
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
AF:
0.200
AC:
30408
AN:
152068
Hom.:
3275
Cov.:
32
AF XY:
0.198
AC XY:
14700
AN XY:
74350
show subpopulations
African (AFR)
AF:
0.258
AC:
10678
AN:
41454
American (AMR)
AF:
0.153
AC:
2347
AN:
15294
Ashkenazi Jewish (ASJ)
AF:
0.285
AC:
987
AN:
3466
East Asian (EAS)
AF:
0.103
AC:
534
AN:
5166
South Asian (SAS)
AF:
0.184
AC:
885
AN:
4822
European-Finnish (FIN)
AF:
0.147
AC:
1559
AN:
10584
Middle Eastern (MID)
AF:
0.288
AC:
84
AN:
292
European-Non Finnish (NFE)
AF:
0.186
AC:
12649
AN:
67970
Other (OTH)
AF:
0.214
AC:
451
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
1213
2426
3638
4851
6064
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:
0.193
Hom.:
366
Bravo
AF:
0.201
Asia WGS
AF:
0.146
AC:
512
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
9.9
DANN
Benign
0.66
PhyloP100
0.072
PromoterAI
0.24
Neutral

Splicing

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

Publications

Other links and lift over

dbSNP: rs422858; hg19: chr3-148415484; API