rs5185

Variant names:

• chr3-148742185-T-G
• rs5185
• NM_000685.5:c.*70T>G

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.*70T>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 0.00466 in 1,579,208 control chromosomes in the GnomAD database, including 286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (167 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (119 hom.)
• Consequence: AGTR1 NM_000685.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.611
• Publications: 10 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=-0.83).
• BP6: Variant 3-148742185-T-G is Benign according to our data. Variant chr3-148742185-T-G is described in ClinVar as Benign. ClinVar VariationId is 343677.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0804 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	NM_000685.5	MANE Select	c.*70T>G		3_prime_UTR	Exon 3 of 3	NP_000676.1
	AGTR1	NM_001382736.1		c.*70T>G		3_prime_UTR	Exon 2 of 2	NP_001369665.1
	AGTR1	NM_001382737.1		c.*70T>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.*70T>G		3_prime_UTR	Exon 3 of 3	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.*70T>G		3_prime_UTR	Exon 2 of 2	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.*70T>G		3_prime_UTR	Exon 2 of 2	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.0241 AC: 3666 AN: 152106 Hom.: 165 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000294

Gnomad OTH AF: 0.0168

GnomAD2 exomes AF: 0.00666 AC: 1661 AN: 249236 AF XY: 0.00500

Gnomad AFR exome AF: 0.0851

Gnomad AMR exome AF: 0.00837

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00578

GnomAD4 exome AF: 0.00258 AC: 3677 AN: 1426984 Hom.: 119 Cov.: 27 AF XY: 0.00223 AC XY: 1591 AN XY: 712350

African (AFR) AF: 0.0806 AC: 2620 AN: 32512

American (AMR) AF: 0.00925 AC: 413 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.0000386 AC: 1 AN: 25940

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.000199 AC: 17 AN: 85260

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00474 AC: 27 AN: 5696

European-Non Finnish (NFE) AF: 0.000221 AC: 239 AN: 1080750

Other (OTH) AF: 0.00607 AC: 360 AN: 59262

GnomAD4 genome AF: 0.0242 AC: 3679 AN: 152224 Hom.: 167 Cov.: 32 AF XY: 0.0239 AC XY: 1776 AN XY: 74438

African (AFR) AF: 0.0827 AC: 3431 AN: 41508

American (AMR) AF: 0.0117 AC: 179 AN: 15286

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 68030

Other (OTH) AF: 0.0166 AC: 35 AN: 2110

Alfa AF: 0.0176 Hom.: 45

Bravo AF: 0.0270

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.53
PhyloP100		0.61
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: rs5185; hg19: chr3-148459972;