3-148708685-T-C

Variant names:

• chr3-148708685-T-C
• rs3772630
• NM_000685.5:c.-48+658T>C

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+658T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 152,016 control chromosomes in the GnomAD database, including 16,060 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 0.43 (16060 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.616
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000685.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	NM_000685.5	MANE Select	c.-48+658T>C		intron	N/A	NP_000676.1
	AGTR1	NM_001382736.1		c.-48+10536T>C		intron	N/A	NP_001369665.1
	AGTR1	NM_001382737.1		c.-48+658T>C		intron	N/A	NP_001369666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.-48+658T>C		intron	N/A	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.-48+10536T>C		intron	N/A	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.-48+10558T>C		intron	N/A	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65715 AN: 151898 Hom.: 16024 Cov.: 32

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.273

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.433 AC: 65798 AN: 152016 Hom.: 16060 Cov.: 32 AF XY: 0.430 AC XY: 31971 AN XY: 74310

African (AFR) AF: 0.682 AC: 28261 AN: 41462

American (AMR) AF: 0.378 AC: 5769 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 946 AN: 3466

East Asian (EAS) AF: 0.377 AC: 1948 AN: 5164

South Asian (SAS) AF: 0.405 AC: 1948 AN: 4814

European-Finnish (FIN) AF: 0.328 AC: 3465 AN: 10580

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22160 AN: 67952

Other (OTH) AF: 0.417 AC: 880 AN: 2110

Alfa AF: 0.356 Hom.: 4935

Bravo AF: 0.445

Asia WGS AF: 0.416 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.2
DANN	Benign	0.72
PhyloP100		0.62
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: rs3772630; hg19: chr3-148426472;