rs275653

Positions:

• chr3-148697758-A-G
• chr3-148697758-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 3-148697758-A-G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,170 control chromosomes in the GnomAD database, including 3,312 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3310 hom., cov: 32)
  • Exomes 𝑓: 0.23 (2 hom.)
• Consequence: AGTR1 ENST00000497524.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000497524.5			upstream_gene_variant		1		ENSP00000419422	P1

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30433 AN: 152012 Hom.: 3299 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.290

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.216

GnomAD4 exome AF: 0.225 AC: 9 AN: 40 Hom.: 2 Cov.: 0 AF XY: 0.265 AC XY: 9 AN XY: 34

Gnomad4 AMR exome AF: 0.500

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.200 AC: 30468 AN: 152130 Hom.: 3310 Cov.: 32 AF XY: 0.198 AC XY: 14730 AN XY: 74362

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.286

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.214

Alfa AF: 0.0671 Hom.: 66

Bravo AF: 0.201

Asia WGS AF: 0.146 AC: 513 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs275653; hg19: chr3-148415545;