dbSNP rs387967: AGTR1:c.-561G>C (chr3-148697698-G-C) – 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.-561G>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 152,074 control chromosomes in the GnomAD database, including 3,273 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 ( 3273 hom., cov: 32)

Exomes 𝑓: 0.083 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

AGTR1
NM_000685.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.408

Publications

5 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5 link	c.-561G>C		upstream_gene_variant		ENST00000349243.8	NP_000676.1	P30556Q53YY0

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
AGTR1	ENST00000349243.8 link	c.-561G>C	upstream_gene_variant	1	NM_000685.5	ENSP00000273430.3	P30556
AGTR1	ENST00000404754.2 link	c.-499G>C	upstream_gene_variant	1		ENSP00000385612.2	P30556
AGTR1	ENST00000497524.5 link	c.-477G>C	upstream_gene_variant	1		ENSP00000419422.1	P30556
AGTR1	ENST00000418473.7 link	c.-535G>C	upstream_gene_variant	5		ENSP00000398832.4	P30556D3DNG8

Frequencies

GnomAD3 genomes

AF:

0.200

AC:

30367

AN:

151956

Hom.:

3262

Cov.:

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:

AN:

Hom.:

AF XY:

0.0714

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.125

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.750

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.200

AC:

30402

AN:

152074

Hom.:

3273

Cov.:

AF XY:

0.198

AC XY:

14697

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.257

AC:

10675

AN:

41458

American (AMR)

AF:

0.153

AC:

2346

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

987

AN:

3466

East Asian (EAS)

AF:

0.103

AC:

534

AN:

5168

South Asian (SAS)

AF:

0.183

AC:

885

AN:

4828

European-Finnish (FIN)

AF:

0.147

AC:

1559

AN:

10576

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.186

AC:

12648

AN:

67978

Other (OTH)

AF:

0.214

AC:

450

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1211

2421

3632

4842

6053

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:

0.193

Hom.:

366

Bravo

AF:

0.201

Asia WGS

AF:

0.146

AC:

512

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.41

PromoterAI

0.52

Over-expression

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over