3-148735539-A-G

Variant names:

• chr3-148735539-A-G
• rs275649
• NM_000685.5:c.-47-5450A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000685.5(AGTR1):​c.-47-5450A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.67 in 152,060 control chromosomes in the GnomAD database, including 36,246 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 0.67 (36246 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.276
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-47-5450A>G		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.-47-5450A>G		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101862 AN: 151942 Hom.: 36231 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.669

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.695

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

GnomAD4 genome AF: 0.670 AC: 101903 AN: 152060 Hom.: 36246 Cov.: 32 AF XY: 0.680 AC XY: 50529 AN XY: 74312

African (AFR) AF: 0.402 AC: 16655 AN: 41462

American (AMR) AF: 0.778 AC: 11882 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2475 AN: 3470

East Asian (EAS) AF: 0.908 AC: 4701 AN: 5178

South Asian (SAS) AF: 0.837 AC: 4036 AN: 4824

European-Finnish (FIN) AF: 0.817 AC: 8628 AN: 10566

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51268 AN: 67976

Other (OTH) AF: 0.699 AC: 1473 AN: 2108

Alfa AF: 0.743 Hom.: 41515

Bravo AF: 0.654

Asia WGS AF: 0.842 AC: 2922 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.1
DANN	Benign	0.72
PhyloP100		0.28
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: rs275649; hg19: chr3-148453326;