NM_000685.5:c.*437G>T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000685.5(AGTR1):​c.*437G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 317,050 control chromosomes in the GnomAD database, including 902 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.077 (598 hom., cov: 33)
  • Exomes 𝑓: 0.053 (304 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 3-148742552-G-T is Benign according to our data. Variant chr3-148742552-G-T is described in ClinVar as Benign. ClinVar VariationId is 343683.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 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.*437G>T		3_prime_UTR	Exon 3 of 3	NP_000676.1	P30556
	AGTR1	NM_001382736.1		c.*437G>T		3_prime_UTR	Exon 2 of 2	NP_001369665.1	Q53YY0
	AGTR1	NM_001382737.1		c.*437G>T		3_prime_UTR	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.*437G>T		3_prime_UTR	Exon 3 of 3	ENSP00000273430.3	P30556
	AGTR1	ENST00000404754.2	TSL:1	c.*437G>T		3_prime_UTR	Exon 2 of 2	ENSP00000385612.2	P30556
	AGTR1	ENST00000497524.5	TSL:1	c.*437G>T		3_prime_UTR	Exon 2 of 2	ENSP00000419422.1	P30556

Frequencies

GnomAD3 genomes AF: 0.0768 AC: 11677 AN: 152006 Hom.: 594 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0669

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0439

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0555

Gnomad OTH AF: 0.0574

GnomAD4 exome AF: 0.0531 AC: 8754 AN: 164926 Hom.: 304 Cov.: 0 AF XY: 0.0512 AC XY: 4567 AN XY: 89132

African (AFR) AF: 0.141 AC: 476 AN: 3382

American (AMR) AF: 0.0324 AC: 175 AN: 5396

Ashkenazi Jewish (ASJ) AF: 0.0294 AC: 105 AN: 3576

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

South Asian (SAS) AF: 0.0447 AC: 1308 AN: 29234

European-Finnish (FIN) AF: 0.0694 AC: 1527 AN: 22016

Middle Eastern (MID) AF: 0.0401 AC: 22 AN: 548

European-Non Finnish (NFE) AF: 0.0545 AC: 4762 AN: 87454

Other (OTH) AF: 0.0509 AC: 379 AN: 7448

GnomAD4 genome AF: 0.0769 AC: 11696 AN: 152124 Hom.: 598 Cov.: 33 AF XY: 0.0761 AC XY: 5659 AN XY: 74366

African (AFR) AF: 0.143 AC: 5941 AN: 41480

American (AMR) AF: 0.0415 AC: 634 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0303 AC: 105 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0436 AC: 210 AN: 4820

European-Finnish (FIN) AF: 0.0789 AC: 834 AN: 10574

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0555 AC: 3776 AN: 67994

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0451 Hom.: 82

Bravo AF: 0.0778

Asia WGS AF: 0.0180 AC: 63 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		0.49
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: rs5189; hg19: chr3-148460339;