rs5184

Variant names:

• chr3-148742117-A-G
• rs5184
• NM_000685.5:c.*2A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_000685.5(AGTR1):​c.*2A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000459 in 1,614,076 control chromosomes in the GnomAD database, including 8 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 0.0025 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (1 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.651
• 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=-0.82).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00255 (388/152234) while in subpopulation AFR AF = 0.0091 (378/41528). AF 95% confidence interval is 0.00835. There are 7 homozygotes in GnomAd4. There are 178 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR,Unknown gene

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.*2A>G		3_prime_UTR	Exon 3 of 3	NP_000676.1
	AGTR1	NM_001382736.1		c.*2A>G		3_prime_UTR	Exon 2 of 2	NP_001369665.1
	AGTR1	NM_001382737.1		c.*2A>G		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.*2A>G		3_prime_UTR	Exon 3 of 3	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.*2A>G		3_prime_UTR	Exon 2 of 2	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.*2A>G		3_prime_UTR	Exon 2 of 2	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 384 AN: 152116 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00903

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000588 AC: 147 AN: 250112 AF XY: 0.000457

Gnomad AFR exome AF: 0.00864

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000883

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000241 AC: 353 AN: 1461842 Hom.: 1 Cov.: 34 AF XY: 0.000204 AC XY: 148 AN XY: 727224

African (AFR) AF: 0.00899 AC: 301 AN: 33476

American (AMR) AF: 0.000425 AC: 19 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111976

Other (OTH) AF: 0.000430 AC: 26 AN: 60396

GnomAD4 genome AF: 0.00255 AC: 388 AN: 152234 Hom.: 7 Cov.: 32 AF XY: 0.00239 AC XY: 178 AN XY: 74444

African (AFR) AF: 0.00910 AC: 378 AN: 41528

American (AMR) AF: 0.000327 AC: 5 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68020

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00127 Hom.: 2

Bravo AF: 0.00266

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism

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: rs5184; hg19: chr3-148459904; COSMIC: COSV100837088;