rs3772616

Variant names:

• chr3-148720404-C-T
• rs3772616
• NM_000685.5:c.-48+12377C>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+12377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,058 control chromosomes in the GnomAD database, including 13,080 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 0.35 (13080 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• Publications: 17 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+12377C>T		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+12377C>T		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52530 AN: 151940 Hom.: 13040 Cov.: 32

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.275

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.346 AC: 52635 AN: 152058 Hom.: 13080 Cov.: 32 AF XY: 0.341 AC XY: 25354 AN XY: 74304

African (AFR) AF: 0.712 AC: 29503 AN: 41440

American (AMR) AF: 0.275 AC: 4207 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 505 AN: 3470

East Asian (EAS) AF: 0.198 AC: 1025 AN: 5178

South Asian (SAS) AF: 0.308 AC: 1483 AN: 4820

European-Finnish (FIN) AF: 0.183 AC: 1935 AN: 10570

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13021 AN: 67988

Other (OTH) AF: 0.311 AC: 657 AN: 2112

Alfa AF: 0.241 Hom.: 11301

Bravo AF: 0.370

Asia WGS AF: 0.306 AC: 1059 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.64
PhyloP100		0.30
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: rs3772616; hg19: chr3-148438191;