3-148742552-G-A

Variant names:

• chr3-148742552-G-A
• rs5189
• NM_000685.5:c.*437G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000685.5(AGTR1):​c.*437G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 317,048 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000072 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000073 (0 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.486
• Publications: 12 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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.*437G>A		3_prime_UTR	Exon 3 of 3	NP_000676.1
	AGTR1	NM_001382736.1		c.*437G>A		3_prime_UTR	Exon 2 of 2	NP_001369665.1
	AGTR1	NM_001382737.1		c.*437G>A		3_prime_UTR	Exon 3 of 3	NP_001369666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.*437G>A		3_prime_UTR	Exon 3 of 3	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.*437G>A		3_prime_UTR	Exon 2 of 2	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.*437G>A		3_prime_UTR	Exon 2 of 2	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.0000724 AC: 11 AN: 152036 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.000478

GnomAD4 exome AF: 0.0000727 AC: 12 AN: 165012 Hom.: 0 Cov.: 0 AF XY: 0.0000673 AC XY: 6 AN XY: 89174

African (AFR) AF: 0.00 AC: 0 AN: 3384

American (AMR) AF: 0.000556 AC: 3 AN: 5400

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3578

East Asian (EAS) AF: 0.00 AC: 0 AN: 5872

South Asian (SAS) AF: 0.0000684 AC: 2 AN: 29244

European-Finnish (FIN) AF: 0.000227 AC: 5 AN: 22034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 548

European-Non Finnish (NFE) AF: 0.0000114 AC: 1 AN: 87496

Other (OTH) AF: 0.000134 AC: 1 AN: 7456

GnomAD4 genome AF: 0.0000724 AC: 11 AN: 152036 Hom.: 0 Cov.: 33 AF XY: 0.0000808 AC XY: 6 AN XY: 74256

African (AFR) AF: 0.0000242 AC: 1 AN: 41372

American (AMR) AF: 0.000196 AC: 3 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68010

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.00 Hom.: 82

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.83
PhyloP100		0.49

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: rs5189; hg19: chr3-148460339;