3-148740058-T-C

Position:

• chr3-148740058-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.-47-931T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,041,846 control chromosomes in the GnomAD database, including 2,445 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.079 (1615 hom., cov: 33)
  • Exomes 𝑓: 0.0079 (830 hom.)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.658

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=-0.62).
• BP6: Variant 3-148740058-T-C is Benign according to our data. Variant chr3-148740058-T-C is described in ClinVar as [Benign]. Clinvar id is 1232440.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.-47-931T>C		intron_variant		ENST00000349243.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGTR1	ENST00000349243.8	c.-47-931T>C		intron_variant		1	NM_000685.5	P1

Frequencies

GnomAD3 genomes AF: 0.0789 AC: 12003 AN: 152124 Hom.: 1618 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0279

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0473

GnomAD4 exome AF: 0.00785 AC: 6985 AN: 889604 Hom.: 830 AF XY: 0.00723 AC XY: 3069 AN XY: 424594

Gnomad4 AFR exome AF: 0.289

Gnomad4 AMR exome AF: 0.0228

Gnomad4 ASJ exome AF: 0.0000753

Gnomad4 EAS exome AF: 0.0000390

Gnomad4 SAS exome AF: 0.000321

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000549

Gnomad4 OTH exome AF: 0.0201

GnomAD4 genome AF: 0.0790 AC: 12022 AN: 152242 Hom.: 1615 Cov.: 33 AF XY: 0.0753 AC XY: 5606 AN XY: 74446

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.0278

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000911

Gnomad4 OTH AF: 0.0468

Alfa AF: 0.0621 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	-0.62
CADD	Benign	7.2
DANN	Benign	0.90

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: rs12695921; hg19: chr3-148457845;