3-148699255-C-G

Variant names:

• chr3-148699255-C-G
• rs2640539
• NM_000685.5:c.-132+1128C>G

Variant summary

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

The NM_000685.5(AGTR1):​c.-132+1128C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,068 control chromosomes in the GnomAD database, including 45,605 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 0.77 (45605 hom., cov: 31)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.735
• Publications: 4 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: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000685.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	NM_000685.5	MANE Select	c.-132+1128C>G		intron	N/A	NP_000676.1	P30556
	AGTR1	NM_001382736.1		c.-48+1106C>G		intron	N/A	NP_001369665.1	Q53YY0
	AGTR1	NM_001382737.1		c.-132+1106C>G		intron	N/A	NP_001369666.1	P30556

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.-132+1128C>G		intron	N/A	ENSP00000273430.3	P30556
	AGTR1	ENST00000404754.2	TSL:1	c.-48+1106C>G		intron	N/A	ENSP00000385612.2	P30556
	AGTR1	ENST00000497524.5	TSL:1	c.-48+1128C>G		intron	N/A	ENSP00000419422.1	P30556

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116820 AN: 151950 Hom.: 45584 Cov.: 31

Gnomad AFR AF: 0.635

Gnomad AMI AF: 0.744

Gnomad AMR AF: 0.835

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.898

Gnomad SAS AF: 0.810

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.762

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

GnomAD4 genome AF: 0.769 AC: 116873 AN: 152068 Hom.: 45605 Cov.: 31 AF XY: 0.771 AC XY: 57303 AN XY: 74334

African (AFR) AF: 0.634 AC: 26293 AN: 41444

American (AMR) AF: 0.835 AC: 12764 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2478 AN: 3470

East Asian (EAS) AF: 0.897 AC: 4641 AN: 5172

South Asian (SAS) AF: 0.812 AC: 3901 AN: 4806

European-Finnish (FIN) AF: 0.852 AC: 9010 AN: 10576

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55288 AN: 67998

Other (OTH) AF: 0.764 AC: 1613 AN: 2110

Alfa AF: 0.751 Hom.: 2430

Bravo AF: 0.763

Asia WGS AF: 0.842 AC: 2925 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.5
DANN	Benign	0.58
PhyloP100		0.73
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: rs2640539; hg19: chr3-148417042;