3-148717966-T-C

Position:

• chr3-148717966-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000685.5(AGTR1):​c.-48+9939T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,080 control chromosomes in the GnomAD database, including 10,848 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 0.34 (10848 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+9939T>C		intron_variant		ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-48+9939T>C		intron_variant		1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52282 AN: 151962 Hom.: 10849 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.344 AC: 52272 AN: 152080 Hom.: 10848 Cov.: 32 AF XY: 0.348 AC XY: 25849 AN XY: 74332

Gnomad4 AFR AF: 0.0946

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.441

Gnomad4 SAS AF: 0.324

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.351

Alfa AF: 0.384 Hom.: 6356

Bravo AF: 0.332

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	18
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs3772622; hg19: chr3-148435753;