rs380400

Positions:

• chr3-148742913-G-A
• chr3-148742913-G-T

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.*798G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.727 in 166,080 control chromosomes in the GnomAD database, including 47,848 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (42990 hom., cov: 31)
  • Exomes 𝑓: 0.82 (4858 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.446

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 3-148742913-G-A is Benign according to our data. Variant chr3-148742913-G-A is described in ClinVar as [Benign]. Clinvar id is 343686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.864 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.*798G>A		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	c.*798G>A		3_prime_UTR_variant	3/3	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.719 AC: 108924 AN: 151512 Hom.: 42977 Cov.: 31

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.811

Gnomad AMR AF: 0.856

Gnomad ASJ AF: 0.903

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.697

Gnomad FIN AF: 0.819

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.870

Gnomad OTH AF: 0.770

GnomAD4 exome AF: 0.819 AC: 11843 AN: 14452 Hom.: 4858 Cov.: 0 AF XY: 0.820 AC XY: 5616 AN XY: 6852

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.819

Gnomad4 NFE exome AF: 0.864

Gnomad4 OTH exome AF: 0.886

GnomAD4 genome AF: 0.719 AC: 108954 AN: 151628 Hom.: 42990 Cov.: 31 AF XY: 0.719 AC XY: 53319 AN XY: 74132

Gnomad4 AFR AF: 0.359

Gnomad4 AMR AF: 0.856

Gnomad4 ASJ AF: 0.903

Gnomad4 EAS AF: 0.838

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.819

Gnomad4 NFE AF: 0.870

Gnomad4 OTH AF: 0.773

Alfa AF: 0.843 Hom.: 43738

Bravo AF: 0.710

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

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.23
DANN	Benign	0.36

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: rs380400; hg19: chr3-148460700;