rs6801836

Positions:

• chr3-148737750-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.-47-3239T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,014 control chromosomes in the GnomAD database, including 5,618 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 0.26 (5618 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-47-3239T>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.-47-3239T>C		intron_variant		1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39260 AN: 151896 Hom.: 5608 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.259 AC: 39299 AN: 152014 Hom.: 5618 Cov.: 32 AF XY: 0.252 AC XY: 18723 AN XY: 74304

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.236

Alfa AF: 0.238 Hom.: 4462

Bravo AF: 0.268

Asia WGS AF: 0.129 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.64

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: rs6801836; hg19: chr3-148455537;