rs12695895

Variant names:

• chr3-148725481-C-T
• rs12695895
• NM_000685.5:c.-47-15508C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000685.5(AGTR1):​c.-47-15508C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.303 in 151,922 control chromosomes in the GnomAD database, including 9,224 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 0.30 (9224 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-47-15508C>T		intron_variant	Intron 2 of 2	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-47-15508C>T		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.303 AC: 45974 AN: 151804 Hom.: 9201 Cov.: 32

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.119

Gnomad EAS AF: 0.133

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.303 AC: 46058 AN: 151922 Hom.: 9224 Cov.: 32 AF XY: 0.300 AC XY: 22292 AN XY: 74252

African (AFR) AF: 0.577 AC: 23888 AN: 41386

American (AMR) AF: 0.253 AC: 3868 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 414 AN: 3466

East Asian (EAS) AF: 0.132 AC: 686 AN: 5180

South Asian (SAS) AF: 0.278 AC: 1337 AN: 4816

European-Finnish (FIN) AF: 0.207 AC: 2177 AN: 10530

Middle Eastern (MID) AF: 0.216 AC: 63 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12865 AN: 67972

Other (OTH) AF: 0.272 AC: 572 AN: 2100

Alfa AF: 0.264 Hom.: 862

Bravo AF: 0.319

Asia WGS AF: 0.247 AC: 858 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.70
PhyloP100		-0.15
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: rs12695895; hg19: chr3-148443268; COSMIC: COSV62559581; COSMIC: COSV62559581;