rs385338

Positions:

• chr3-148731369-C-G
• chr3-148731369-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.-47-9620C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 152,046 control chromosomes in the GnomAD database, including 43,083 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 0.73 (43083 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-47-9620C>G		intron_variant		ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-47-9620C>G		intron_variant		1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111619 AN: 151928 Hom.: 43069 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.768

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.895

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.756

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.734 AC: 111662 AN: 152046 Hom.: 43083 Cov.: 32 AF XY: 0.742 AC XY: 55200 AN XY: 74348

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.768

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.865

Gnomad4 FIN AF: 0.895

Gnomad4 NFE AF: 0.831

Gnomad4 OTH AF: 0.759

Alfa AF: 0.777 Hom.: 5858

Bravo AF: 0.715

Asia WGS AF: 0.834 AC: 2891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.0060
DANN	Benign	0.48

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: rs385338; hg19: chr3-148449156;