chr3-148726850-G-A

Variant names:

• chr3-148726850-G-A
• rs16860760
• NM_000685.5:c.-47-14139G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_000685.5(AGTR1):​c.-47-14139G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00656 in 152,252 control chromosomes in the GnomAD database, including 22 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 0.0066 (22 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.605
• Publications: 7 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0598 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	NM_000685.5	MANE Select	c.-47-14139G>A		intron	N/A	NP_000676.1
	AGTR1	NM_001382736.1		c.-47-14139G>A		intron	N/A	NP_001369665.1
	AGTR1	NM_001382737.1		c.-47-14139G>A		intron	N/A	NP_001369666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.-47-14139G>A		intron	N/A	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.-47-14139G>A		intron	N/A	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.-47-14139G>A		intron	N/A	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.00657 AC: 1000 AN: 152134 Hom.: 22 Cov.: 32

Gnomad AFR AF: 0.000942

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.0257

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.0280

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00196

Gnomad OTH AF: 0.0134

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

GnomAD4 genome AF: 0.00656 AC: 999 AN: 152252 Hom.: 22 Cov.: 32 AF XY: 0.00739 AC XY: 550 AN XY: 74448

African (AFR) AF: 0.000963 AC: 40 AN: 41540

American (AMR) AF: 0.0126 AC: 193 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0257 AC: 89 AN: 3468

East Asian (EAS) AF: 0.0655 AC: 339 AN: 5172

South Asian (SAS) AF: 0.0278 AC: 134 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00196 AC: 133 AN: 68010

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00437 Hom.: 6

Bravo AF: 0.00679

Asia WGS AF: 0.0470 AC: 164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		0.60
Mutation Taster		=100/0	polymorphism

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: rs16860760; hg19: chr3-148444637;