Variant 3-148742552-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000685.5(AGTR1):c.*437G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 317,050 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 598 hom., cov: 33)

Exomes 𝑓: 0.053 ( 304 hom. )

Consequence

AGTR1
NM_000685.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.486

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 3-148742552-G-T is Benign according to our data. Variant chr3-148742552-G-T is described in ClinVar as [Benign]. Clinvar id is 343683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5 linkuse as main transcript	c.*437G>T		3_prime_UTR_variant	3/3	ENST00000349243.8	NP_000676.1	P30556Q53YY0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8 linkuse as main transcript	c.*437G>T		3_prime_UTR_variant	3/3	1	NM_000685.5	ENSP00000273430.3		P30556

Frequencies

GnomAD3 genomes

AF:

0.0768

AC:

11677

AN:

152006

Hom.:

594

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0416

Gnomad ASJ

AF:

0.0303

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0439

Gnomad FIN

AF:

0.0789

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.0555

Gnomad OTH

AF:

0.0574

GnomAD4 exome

AF:

0.0531

AC:

8754

AN:

164926

Hom.:

304

Cov.:

AF XY:

0.0512

AC XY:

4567

AN XY:

89132

show subpopulations

Gnomad4 AFR exome

AF:

0.141

Gnomad4 AMR exome

AF:

0.0324

Gnomad4 ASJ exome

AF:

0.0294

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0447

Gnomad4 FIN exome

AF:

0.0694

Gnomad4 NFE exome

AF:

0.0545

Gnomad4 OTH exome

AF:

0.0509

GnomAD4 genome

AF:

0.0769

AC:

11696

AN:

152124

Hom.:

598

Cov.:

AF XY:

0.0761

AC XY:

5659

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.0415

Gnomad4 ASJ

AF:

0.0303

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0436

Gnomad4 FIN

AF:

0.0789

Gnomad4 NFE

AF:

0.0555

Gnomad4 OTH

AF:

0.0568

Alfa

AF:

0.0290

Hom.:

Bravo

AF:

0.0778

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Renal tubular dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.2

DANN

Benign

0.65

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over