chr3-148739686-T-C

Position:

• chr3-148739686-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000685.5(AGTR1):​c.-47-1303T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,033,208 control chromosomes in the GnomAD database, including 2,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (1611 hom., cov: 32)
  • Exomes 𝑓: 0.0076 (787 hom.)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.150

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-148739686-T-C is Benign according to our data. Variant chr3-148739686-T-C is described in ClinVar as [Benign]. Clinvar id is 1220644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGTR1	NM_000685.5	c.-47-1303T>C		intron_variant		ENST00000349243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTR1	ENST00000349243.8	c.-47-1303T>C		intron_variant		1	NM_000685.5	P1

Frequencies

GnomAD3 genomes AF: 0.0788 AC: 11990 AN: 152120 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.00760 AC: 6692 AN: 880970 Hom.: 787 AF XY: 0.00699 AC XY: 2940 AN XY: 420636

Gnomad4 AFR exome AF: 0.283

Gnomad4 AMR exome AF: 0.0226

Gnomad4 ASJ exome AF: 0.0000763

Gnomad4 EAS exome AF: 0.0000394

Gnomad4 SAS exome AF: 0.000272

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000523

Gnomad4 OTH exome AF: 0.0201

GnomAD4 genome AF: 0.0789 AC: 12009 AN: 152238 Hom.: 1611 Cov.: 32 AF XY: 0.0752 AC XY: 5597 AN XY: 74440

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000912

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0619 Hom.: 119

Bravo AF: 0.0898

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
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: rs12721291; hg19: chr3-148457473;