rs5185

chr3-148742185-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000685.5(AGTR1):c.*70T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00466 in 1,579,208 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (167 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (119 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.611

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-148742185-T-G is Benign according to our data. Variant chr3-148742185-T-G is described in ClinVar as [Benign]. Clinvar id is 343677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTR1	NM_000685.5	c.*70T>G		3_prime_UTR_variant	3/3	ENST00000349243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTR1	ENST00000349243.8	c.*70T>G		3_prime_UTR_variant	3/3	1	NM_000685.5	P1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3666 AN: 152106 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0168

GnomAD3 exomes AF: 0.00666 AC: 1661 AN: 249236 Hom.: 60 AF XY: 0.00500 AC XY: 677 AN XY: 135296

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.00837

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00578

GnomAD4 exome AF: 0.00258 AC: 3677 AN: 1426984 Hom.: 119 Cov.: 27 AF XY: 0.00223 AC XY: 1591 AN XY: 712350

Gnomad4 AFR exome AF: 0.0806

Gnomad4 AMR exome AF: 0.00925

Gnomad4 ASJ exome AF: 0.0000386

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000199

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000221

Gnomad4 OTH exome AF: 0.00607

GnomAD4 genome AF: 0.0242 AC: 3679 AN: 152224 Hom.: 167 Cov.: 32 AF XY: 0.0239 AC XY: 1776 AN XY: 74438

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000294

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0205 Hom.: 31

Bravo AF: 0.0270

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal tubular dysgenesis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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

clinical testing

GeneDx

Jun 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	3.1
Dann	Benign	0.53

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

Other links and lift over

dbSNP: rs5185; hg19: chr3-148459972;