3-148709247-T-C

Position:

• chr3-148709247-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+1220T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,848 control chromosomes in the GnomAD database, including 16,065 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 0.43 (16065 hom., cov: 31)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.221

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+1220T>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+1220T>C		intron_variant		1	NM_000685.5	ENSP00000273430	P1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65774 AN: 151730 Hom.: 16032 Cov.: 31

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.274

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.434 AC: 65852 AN: 151848 Hom.: 16065 Cov.: 31 AF XY: 0.431 AC XY: 31990 AN XY: 74206

Gnomad4 AFR AF: 0.681

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.274

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.406

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.417

Alfa AF: 0.365 Hom.: 5309

Bravo AF: 0.445

Asia WGS AF: 0.415 AC: 1440 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.3
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12695877; hg19: chr3-148427034;