dbSNP rs385338: AGTR1:c.-47-9620C>G (chr3-148731369-C-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.-47-9620C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,046 control chromosomes in the GnomAD database, including 43,083 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 0.73 ( 43083 hom., cov: 32)

Failed GnomAD Quality Control

Consequence

AGTR1
NM_000685.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81

Publications

11 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=-0.94).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5 link	c.-47-9620C>G		intron_variant	Intron 2 of 2	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8 link	c.-47-9620C>G		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes

AF:

0.735

AC:

111619

AN:

151928

Hom.:

43069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.692

Gnomad AMR

AF:

0.829

Gnomad ASJ

AF:

0.768

Gnomad EAS

AF:

0.844

Gnomad SAS

AF:

0.864

Gnomad FIN

AF:

0.895

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.831

Gnomad OTH

AF:

0.756

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AC:

AN:

Hom.:

Cov.:

AC XY:

AN XY:

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)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.734

AC:

111662

AN:

152046

Hom.:

43083

Cov.:

AF XY:

0.742

AC XY:

55200

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.468

AC:

19362

AN:

41416

American (AMR)

AF:

0.829

AC:

12670

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.768

AC:

2665

AN:

3472

East Asian (EAS)

AF:

0.843

AC:

4357

AN:

5166

South Asian (SAS)

AF:

0.865

AC:

4182

AN:

4834

European-Finnish (FIN)

AF:

0.895

AC:

9476

AN:

10582

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.831

AC:

56505

AN:

67984

Other (OTH)

AF:

0.759

AC:

1604

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1327

2655

3982

5310

6637

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.777

Hom.:

5858

Bravo

AF:

0.715

Asia WGS

AF:

0.834

AC:

2891

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.0060

(source)

DANN

Benign

0.48

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(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

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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