NM_000685.5:c.573C>T

Variant names:

• chr3-148741608-C-T
• rs5182
• NM_000685.5:c.573C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000685.5(AGTR1):​c.573C>T​(p.Leu191Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 1,613,482 control chromosomes in the GnomAD database, including 180,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (14558 hom., cov: 32)
  • Exomes 𝑓: 0.47 (166368 hom.)
• Consequence: AGTR1 NM_000685.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.186
• Publications: 106 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• essential hypertension, genetic

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

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 3-148741608-C-T is Benign according to our data. Variant chr3-148741608-C-T is described in ClinVar as Benign. ClinVar VariationId is 256759.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.186 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.666 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	NM_000685.5	MANE Select	c.573C>T	p.Leu191Leu	synonymous	Exon 3 of 3	NP_000676.1	P30556
	AGTR1	NM_001382736.1		c.573C>T	p.Leu191Leu	synonymous	Exon 2 of 2	NP_001369665.1	Q53YY0
	AGTR1	NM_001382737.1		c.573C>T	p.Leu191Leu	synonymous	Exon 3 of 3	NP_001369666.1	P30556

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.573C>T	p.Leu191Leu	synonymous	Exon 3 of 3	ENSP00000273430.3	P30556
	AGTR1	ENST00000404754.2	TSL:1	c.573C>T	p.Leu191Leu	synonymous	Exon 2 of 2	ENSP00000385612.2	P30556
	AGTR1	ENST00000497524.5	TSL:1	c.573C>T	p.Leu191Leu	synonymous	Exon 2 of 2	ENSP00000419422.1	P30556

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62741 AN: 151880 Hom.: 14550 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.259

Gnomad AMR AF: 0.505

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.685

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.585

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.427

GnomAD2 exomes AF: 0.490 AC: 122644 AN: 250128 AF XY: 0.491

Gnomad AFR exome AF: 0.192

Gnomad AMR exome AF: 0.542

Gnomad ASJ exome AF: 0.408

Gnomad EAS exome AF: 0.702

Gnomad FIN exome AF: 0.585

Gnomad NFE exome AF: 0.472

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.473 AC: 690764 AN: 1461484 Hom.: 166368 Cov.: 59 AF XY: 0.473 AC XY: 344192 AN XY: 727038

African (AFR) AF: 0.186 AC: 6217 AN: 33476

American (AMR) AF: 0.537 AC: 24007 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 10514 AN: 26132

East Asian (EAS) AF: 0.675 AC: 26784 AN: 39700

South Asian (SAS) AF: 0.490 AC: 42299 AN: 86250

European-Finnish (FIN) AF: 0.580 AC: 30994 AN: 53394

Middle Eastern (MID) AF: 0.404 AC: 2333 AN: 5768

European-Non Finnish (NFE) AF: 0.468 AC: 519913 AN: 1111686

Other (OTH) AF: 0.459 AC: 27703 AN: 60384

GnomAD4 genome AF: 0.413 AC: 62762 AN: 151998 Hom.: 14558 Cov.: 32 AF XY: 0.422 AC XY: 31312 AN XY: 74286

African (AFR) AF: 0.204 AC: 8441 AN: 41464

American (AMR) AF: 0.505 AC: 7718 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1392 AN: 3466

East Asian (EAS) AF: 0.685 AC: 3535 AN: 5164

South Asian (SAS) AF: 0.492 AC: 2366 AN: 4812

European-Finnish (FIN) AF: 0.585 AC: 6169 AN: 10550

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.469 AC: 31874 AN: 67956

Other (OTH) AF: 0.434 AC: 917 AN: 2112

Alfa AF: 0.446 Hom.: 43449

Bravo AF: 0.398

Asia WGS AF: 0.575 AC: 1998 AN: 3478

EpiCase AF: 0.452

EpiControl AF: 0.449

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Renal tubular dysgenesis (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.61
PhyloP100		-0.19
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: rs5182; hg19: chr3-148459395; COSMIC: COSV62559474;