rs1492097

Positions:

• chr3-148719902-G-A
• chr3-148719902-G-T

Variant summary

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

The NM_000685.5(AGTR1):​c.-48+11875G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,916 control chromosomes in the GnomAD database, including 10,415 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 0.32 (10415 hom., cov: 33)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0560

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+11875G>A		intron_variant		ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-48+11875G>A		intron_variant		1	NM_000685.5	ENSP00000273430	P1

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48146 AN: 151798 Hom.: 10388 Cov.: 33

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.286

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.318 AC: 48237 AN: 151916 Hom.: 10415 Cov.: 33 AF XY: 0.314 AC XY: 23272 AN XY: 74230

Gnomad4 AFR AF: 0.619

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.289

Alfa AF: 0.258 Hom.: 843

Bravo AF: 0.337

Asia WGS AF: 0.254 AC: 881 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.6
DANN	Benign	0.51

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: rs1492097; hg19: chr3-148437689;