NM_000685.5:c.*86A>C

Variant names:

• chr3-148742201-A-C
• rs5186
• NM_000685.5:c.*86A>C

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.*86A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,538,798 control chromosomes in the GnomAD database, including 58,749 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4182 hom., cov: 32)
  • Exomes 𝑓: 0.27 (54567 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4 O:1
• Conservation: PhyloP100: 1.07
• Publications: 986 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-148742201-A-C is Benign according to our data. Variant chr3-148742201-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 18065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.*86A>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.*86A>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31344 AN: 152074 Hom.: 4181 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.474

Gnomad AMR AF: 0.258

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.0566

Gnomad SAS AF: 0.0807

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.296

Gnomad OTH AF: 0.225

GnomAD2 exomes AF: 0.227 AC: 56561 AN: 248638 AF XY: 0.223

Gnomad AFR exome AF: 0.0578

Gnomad AMR exome AF: 0.300

Gnomad ASJ exome AF: 0.308

Gnomad EAS exome AF: 0.0566

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.292

Gnomad OTH exome AF: 0.258

GnomAD4 exome AF: 0.269 AC: 373676 AN: 1386606 Hom.: 54567 Cov.: 24 AF XY: 0.264 AC XY: 183361 AN XY: 694336

African (AFR) AF: 0.0544 AC: 1716 AN: 31540

American (AMR) AF: 0.295 AC: 13154 AN: 44598

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 7919 AN: 25674

East Asian (EAS) AF: 0.0704 AC: 2768 AN: 39302

South Asian (SAS) AF: 0.0920 AC: 7742 AN: 84154

European-Finnish (FIN) AF: 0.196 AC: 10447 AN: 53370

Middle Eastern (MID) AF: 0.197 AC: 1109 AN: 5618

European-Non Finnish (NFE) AF: 0.301 AC: 314568 AN: 1044350

Other (OTH) AF: 0.246 AC: 14253 AN: 58000

GnomAD4 genome AF: 0.206 AC: 31351 AN: 152192 Hom.: 4182 Cov.: 32 AF XY: 0.199 AC XY: 14781 AN XY: 74406

African (AFR) AF: 0.0623 AC: 2590 AN: 41540

American (AMR) AF: 0.258 AC: 3947 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1119 AN: 3470

East Asian (EAS) AF: 0.0569 AC: 295 AN: 5184

South Asian (SAS) AF: 0.0804 AC: 388 AN: 4828

European-Finnish (FIN) AF: 0.179 AC: 1898 AN: 10596

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20153 AN: 67978

Other (OTH) AF: 0.223 AC: 470 AN: 2112

Alfa AF: 0.266 Hom.: 21358

Bravo AF: 0.212

Asia WGS AF: 0.0770 AC: 266 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 17668390, 22237156, 21638051, 20525211, 19021695, 22475523, 18985387, 20703234, 19236533, 19620885, 21799445, 17588946, 21771600, 20026870, 21436209, 22392878, 20594303, 20361261, 21657802, 25603901, 22664914, 8021009, 23615648, 30920415, 27016615, 26283679) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Renal tubular dysgenesis Benign:1

Mar 06, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Renal tubular dysgenesis of genetic origin;CN305331:Essential hypertension, genetic Benign:1

Aug 16, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertension, essential, susceptibility to Other:1

Aug 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.67
PhyloP100		1.1
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: rs5186; hg19: chr3-148459988;