rs1492097

Variant names:

• chr3-148719902-G-A
• rs1492097
• NM_000685.5:c.-48+11875G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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]

AGTR1 Gene-Disease associations (from GenCC):

• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+11875G>A		intron_variant	Intron 2 of 2	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-48+11875G>A		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

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

African (AFR) AF: 0.619 AC: 25657 AN: 41448

American (AMR) AF: 0.259 AC: 3961 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3464

East Asian (EAS) AF: 0.134 AC: 691 AN: 5160

South Asian (SAS) AF: 0.287 AC: 1375 AN: 4788

European-Finnish (FIN) AF: 0.188 AC: 1988 AN: 10552

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13228 AN: 67922

Other (OTH) AF: 0.289 AC: 611 AN: 2112

Alfa AF: 0.275 Hom.: 1014

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
PhyloP100		0.056
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1492097; hg19: chr3-148437689;