rs4524238

Variant names:

• chr3-148722001-G-A
• rs4524238
• NM_000685.5:c.-48+13974G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000685.5(AGTR1):​c.-48+13974G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,988 control chromosomes in the GnomAD database, including 10,262 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 0.31 (10262 hom., cov: 32)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 13 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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+13974G>A		intron_variant	Intron 2 of 2	ENST00000349243.8	NP_000676.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGTR1	ENST00000349243.8	c.-48+13974G>A		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47461 AN: 151870 Hom.: 10236 Cov.: 32

Gnomad AFR AF: 0.619

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.313 AC: 47550 AN: 151988 Hom.: 10262 Cov.: 32 AF XY: 0.309 AC XY: 22928 AN XY: 74310

African (AFR) AF: 0.619 AC: 25643 AN: 41438

American (AMR) AF: 0.255 AC: 3895 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 416 AN: 3470

East Asian (EAS) AF: 0.132 AC: 678 AN: 5152

South Asian (SAS) AF: 0.276 AC: 1325 AN: 4808

European-Finnish (FIN) AF: 0.183 AC: 1937 AN: 10564

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12820 AN: 67962

Other (OTH) AF: 0.277 AC: 584 AN: 2110

Alfa AF: 0.227 Hom.: 19611

Bravo AF: 0.333

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.023
DANN	Benign	0.61
PhyloP100		-1.9
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: rs4524238; hg19: chr3-148439788;