rs12695895

Positions:

• chr3-148725481-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AGTR1	NM_000685.5	c.-47-15508C>T		intron_variant		ENST00000349243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTR1	ENST00000349243.8	c.-47-15508C>T		intron_variant		1	NM_000685.5	P1

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

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.119

Gnomad4 EAS AF: 0.132

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.272

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs12695895; hg19: chr3-148443268; COSMIC: COSV62559581; COSMIC: COSV62559581;