rs909383

Variant names:

• chr3-148718419-C-T
• rs909383
• NM_000685.5:c.-48+10392C>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+10392C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,022 control chromosomes in the GnomAD database, including 9,910 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 0.31 (9910 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.589 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+10392C>T		intron	N/A	NP_000676.1
	AGTR1	NM_001382736.1		c.-48+20270C>T		intron	N/A	NP_001369665.1
	AGTR1	NM_001382737.1		c.-48+10392C>T		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+10392C>T		intron	N/A	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.-48+20270C>T		intron	N/A	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.-48+20292C>T		intron	N/A	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47576 AN: 151904 Hom.: 9885 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.127

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.314 AC: 47661 AN: 152022 Hom.: 9910 Cov.: 32 AF XY: 0.309 AC XY: 22933 AN XY: 74304

African (AFR) AF: 0.595 AC: 24650 AN: 41434

American (AMR) AF: 0.227 AC: 3471 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 475 AN: 3468

East Asian (EAS) AF: 0.126 AC: 654 AN: 5172

South Asian (SAS) AF: 0.292 AC: 1407 AN: 4824

European-Finnish (FIN) AF: 0.190 AC: 2009 AN: 10564

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14079 AN: 67982

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.243 Hom.: 2700

Bravo AF: 0.327

Asia WGS AF: 0.245 AC: 849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.0
DANN	Benign	0.61
PhyloP100		-1.0
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: rs909383; hg19: chr3-148436206;