rs422858

Variant names:

• chr3-148697697-A-C
• rs422858
• NM_000685.5:c.-562A>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000685.5(AGTR1):​c.-562A>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 152,068 control chromosomes in the GnomAD database, including 3,275 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 0.20 (3275 hom., cov: 32)
  • Exomes 𝑓: 0.083 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AGTR1 NM_000685.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.253 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-562A>C		upstream_gene_variant		ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-562A>C		upstream_gene_variant		1	NM_000685.5	ENSP00000273430.3
AGTR1	ENST00000404754.2	c.-500A>C		upstream_gene_variant		1		ENSP00000385612.2
AGTR1	ENST00000497524.5	c.-478A>C		upstream_gene_variant		1		ENSP00000419422.1
AGTR1	ENST00000418473.7	c.-536A>C		upstream_gene_variant		5		ENSP00000398832.4

Frequencies

GnomAD3 genomes AF: 0.200 AC: 30373 AN: 151952 Hom.: 3264 Cov.: 32

Gnomad AFR AF: 0.257

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.283

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.216

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0833 AC: 1 AN: 12 Hom.: 0 AF XY: 0.100 AC XY: 1 AN XY: 10

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.200 AC: 30408 AN: 152068 Hom.: 3275 Cov.: 32 AF XY: 0.198 AC XY: 14700 AN XY: 74350

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.214

Alfa AF: 0.206 Hom.: 302

Bravo AF: 0.201

Asia WGS AF: 0.146 AC: 512 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.9
DANN	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs422858; hg19: chr3-148415484;