rs388915

Positions:

• chr3-148729969-G-A

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.-47-11020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 287,234 control chromosomes in the GnomAD database, including 71,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (34036 hom., cov: 29)
  • Exomes 𝑓: 0.74 (37310 hom.)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.29

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=-0.91).
• BP6: Variant 3-148729969-G-A is Benign according to our data. Variant chr3-148729969-G-A is described in ClinVar as [Benign]. Clinvar id is 1233874.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTR1	NM_000685.5	c.-47-11020G>A		intron_variant		ENST00000349243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTR1	ENST00000349243.8	c.-47-11020G>A		intron_variant		1	NM_000685.5	P1

Frequencies

GnomAD3 genomes AF: 0.649 AC: 98372 AN: 151566 Hom.: 34019 Cov.: 29

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.832

Gnomad FIN AF: 0.805

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.734

Gnomad OTH AF: 0.675

GnomAD4 exome AF: 0.737 AC: 99872 AN: 135550 Hom.: 37310 AF XY: 0.737 AC XY: 51122 AN XY: 69366

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.691

Gnomad4 EAS exome AF: 0.846

Gnomad4 SAS exome AF: 0.821

Gnomad4 FIN exome AF: 0.810

Gnomad4 NFE exome AF: 0.734

Gnomad4 OTH exome AF: 0.706

GnomAD4 genome AF: 0.649 AC: 98412 AN: 151684 Hom.: 34036 Cov.: 29 AF XY: 0.659 AC XY: 48848 AN XY: 74144

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.758

Gnomad4 ASJ AF: 0.703

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.833

Gnomad4 FIN AF: 0.805

Gnomad4 NFE AF: 0.734

Gnomad4 OTH AF: 0.679

Alfa AF: 0.710 Hom.: 22169

Bravo AF: 0.631

Asia WGS AF: 0.811 AC: 2818 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.66

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: rs388915; hg19: chr3-148447756;