rs5186

Positions:

chr3-148742201-A-C

Variant summary

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

The NM_000685.5(AGTR1):c.*86A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,538,798 control chromosomes in the GnomAD database, including 58,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 4182 hom., cov: 32)

Exomes 𝑓: 0.27 ( 54567 hom. )

Consequence

AGTR1
NM_000685.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 1.07

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-148742201-A-C is Benign according to our data. Variant chr3-148742201-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 18065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-148742201-A-C is described in Lovd as [Likely_pathogenic].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 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.*86A>C		3_prime_UTR_variant	3/3	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8 linkuse as main transcript	c.*86A>C		3_prime_UTR_variant	3/3	1	NM_000685.5	ENSP00000273430	P1

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31344

AN:

152074

Hom.:

4181

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.322

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0807

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.296

Gnomad OTH

AF:

0.225

GnomAD3 exomes

AF:

0.227

AC:

56561

AN:

248638

Hom.:

7763

AF XY:

0.223

AC XY:

30159

AN XY:

135076

show subpopulations

Gnomad AFR exome

AF:

0.0578

Gnomad AMR exome

AF:

0.300

Gnomad ASJ exome

AF:

0.308

Gnomad EAS exome

AF:

0.0566

Gnomad SAS exome

AF:

0.0895

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.258

GnomAD4 exome

AF:

0.269

AC:

373676

AN:

1386606

Hom.:

54567

Cov.:

AF XY:

0.264

AC XY:

183361

AN XY:

694336

show subpopulations

Gnomad4 AFR exome

AF:

0.0544

Gnomad4 AMR exome

AF:

0.295

Gnomad4 ASJ exome

AF:

0.308

Gnomad4 EAS exome

AF:

0.0704

Gnomad4 SAS exome

AF:

0.0920

Gnomad4 FIN exome

AF:

0.196

Gnomad4 NFE exome

AF:

0.301

Gnomad4 OTH exome

AF:

0.246

GnomAD4 genome

AF:

0.206

AC:

31351

AN:

152192

Hom.:

4182

Cov.:

AF XY:

0.199

AC XY:

14781

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0623

Gnomad4 AMR

AF:

0.258

Gnomad4 ASJ

AF:

0.322

Gnomad4 EAS

AF:

0.0569

Gnomad4 SAS

AF:

0.0804

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.296

Gnomad4 OTH

AF:

0.223

Alfa

AF:

0.275

Hom.:

10274

Bravo

AF:

0.212

Asia WGS

AF:

0.0770

AC:

266

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	This variant is associated with the following publications: (PMID: 17668390, 22237156, 21638051, 20525211, 19021695, 22475523, 18985387, 20703234, 19236533, 19620885, 21799445, 17588946, 21771600, 20026870, 21436209, 22392878, 20594303, 20361261, 21657802, 25603901, 22664914, 8021009, 23615648, 30920415, 27016615, 26283679) -

Renal tubular dysgenesis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Mar 06, 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. -

Renal tubular dysgenesis of genetic origin;CN305331:Essential hypertension, genetic

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Aug 16, 2021

- -

Hypertension, essential, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Aug 01, 2007

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.67

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