rs2638360

Variant names:

• chr3-148710569-G-A
• rs2638360
• NM_000685.5:c.-48+2542G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-148710569-G-A
• chr3-148710569-G-C
• chr3-148710569-G-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.-48+2542G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.867 in 152,182 control chromosomes in the GnomAD database, including 57,692 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 0.87 (57692 hom., cov: 33)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+2542G>A		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.-48+2542G>A		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.867 AC: 131878 AN: 152064 Hom.: 57623 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.746

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.833

Gnomad FIN AF: 0.838

Gnomad MID AF: 0.787

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.867 AC: 132009 AN: 152182 Hom.: 57692 Cov.: 33 AF XY: 0.868 AC XY: 64542 AN XY: 74390

African (AFR) AF: 0.966 AC: 40155 AN: 41556

American (AMR) AF: 0.882 AC: 13480 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.746 AC: 2588 AN: 3470

East Asian (EAS) AF: 0.930 AC: 4807 AN: 5168

South Asian (SAS) AF: 0.835 AC: 4022 AN: 4818

European-Finnish (FIN) AF: 0.838 AC: 8871 AN: 10582

Middle Eastern (MID) AF: 0.784 AC: 229 AN: 292

European-Non Finnish (NFE) AF: 0.814 AC: 55377 AN: 67996

Other (OTH) AF: 0.842 AC: 1776 AN: 2110

Alfa AF: 0.839 Hom.: 6295

Bravo AF: 0.876

Asia WGS AF: 0.900 AC: 3119 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.21
PhyloP100		-0.094
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: rs2638360; hg19: chr3-148428356;