chr3-148714787-A-C

Variant names:

• chr3-148714787-A-C
• rs4681444
• NM_000685.5:c.-48+6760A>C

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+6760A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,998 control chromosomes in the GnomAD database, including 9,432 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 0.29 (9432 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 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.-48+6760A>C		intron	N/A	NP_000676.1
	AGTR1	NM_001382736.1		c.-48+16638A>C		intron	N/A	NP_001369665.1
	AGTR1	NM_001382737.1		c.-48+6760A>C		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.-48+6760A>C		intron	N/A	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.-48+16638A>C		intron	N/A	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.-48+16660A>C		intron	N/A	ENSP00000419422.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43903 AN: 151880 Hom.: 9400 Cov.: 32

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0644

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.289 AC: 43989 AN: 151998 Hom.: 9432 Cov.: 32 AF XY: 0.285 AC XY: 21162 AN XY: 74292

African (AFR) AF: 0.607 AC: 25131 AN: 41432

American (AMR) AF: 0.179 AC: 2736 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 429 AN: 3466

East Asian (EAS) AF: 0.0640 AC: 331 AN: 5174

South Asian (SAS) AF: 0.235 AC: 1132 AN: 4808

European-Finnish (FIN) AF: 0.166 AC: 1755 AN: 10592

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11627 AN: 67958

Other (OTH) AF: 0.280 AC: 591 AN: 2114

Alfa AF: 0.204 Hom.: 13576

Bravo AF: 0.301

Asia WGS AF: 0.189 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.47
DANN	Benign	0.44
PhyloP100		-1.7
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: rs4681444; hg19: chr3-148432574;