rs2276736

Positions:

• chr3-148708086-A-G
• chr3-148708086-A-T

Variant summary

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

The ENST00000349243.8(AGTR1):​c.-48+59A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 151,810 control chromosomes in the GnomAD database, including 11,689 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 0.38 (11687 hom., cov: 31)
  • Exomes 𝑓: 0.50 (2 hom.)
• Consequence: AGTR1 ENST00000349243.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+59A>G		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+59A>G		intron_variant		1	NM_000685.5	ENSP00000273430	P1

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58249 AN: 151682 Hom.: 11663 Cov.: 31

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.360

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.376

GnomAD4 exome AF: 0.500 AC: 5 AN: 10 Hom.: 2 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.384 AC: 58319 AN: 151800 Hom.: 11687 Cov.: 31 AF XY: 0.383 AC XY: 28380 AN XY: 74182

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.360

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.377

Gnomad4 SAS AF: 0.405

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.380

Alfa AF: 0.343 Hom.: 4789

Bravo AF: 0.390

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.36

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: rs2276736; hg19: chr3-148425873;