rs6801836

Variant names:

• chr3-148737750-T-C
• rs6801836
• NM_000685.5:c.-47-3239T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

AGTR1 Gene-Disease associations (from GenCC):

• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• essential hypertension, genetic

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000685.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	NM_000685.5	MANE Select	c.-47-3239T>C		intron	N/A	NP_000676.1
	AGTR1	NM_001382736.1		c.-47-3239T>C		intron	N/A	NP_001369665.1
	AGTR1	NM_001382737.1		c.-47-3239T>C		intron	N/A	NP_001369666.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.-47-3239T>C		intron	N/A	ENSP00000273430.3
	AGTR1	ENST00000404754.2	TSL:1	c.-47-3239T>C		intron	N/A	ENSP00000385612.2
	AGTR1	ENST00000497524.5	TSL:1	c.-47-3239T>C		intron	N/A	ENSP00000419422.1

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

African (AFR) AF: 0.390 AC: 16148 AN: 41414

American (AMR) AF: 0.206 AC: 3155 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3466

East Asian (EAS) AF: 0.104 AC: 539 AN: 5168

South Asian (SAS) AF: 0.145 AC: 701 AN: 4818

European-Finnish (FIN) AF: 0.173 AC: 1834 AN: 10582

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15268 AN: 67970

Other (OTH) AF: 0.236 AC: 498 AN: 2108

Alfa AF: 0.241 Hom.: 12229

Bravo AF: 0.268

Asia WGS AF: 0.129 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.1
DANN	Benign	0.64
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6801836; hg19: chr3-148455537;