NM_000685.5:c.-48+11689T>C

Variant names:

• chr3-148719716-T-C
• rs1492099
• NM_000685.5:c.-48+11689T>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.-48+11689T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,174 control chromosomes in the GnomAD database, including 60,496 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 0.89 (60496 hom., cov: 31)
• Consequence: AGTR1 NM_000685.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0120
• Publications: 16 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 = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGTR1	NM_000685.5	c.-48+11689T>C		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+11689T>C		intron_variant	Intron 2 of 2	1	NM_000685.5	ENSP00000273430.3

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135271 AN: 152056 Hom.: 60437 Cov.: 31

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.812

Gnomad AMR AF: 0.897

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.929

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.791

Gnomad NFE AF: 0.854

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.890 AC: 135390 AN: 152174 Hom.: 60496 Cov.: 31 AF XY: 0.889 AC XY: 66094 AN XY: 74378

African (AFR) AF: 0.968 AC: 40218 AN: 41540

American (AMR) AF: 0.897 AC: 13715 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2759 AN: 3470

East Asian (EAS) AF: 0.929 AC: 4777 AN: 5142

South Asian (SAS) AF: 0.841 AC: 4047 AN: 4814

European-Finnish (FIN) AF: 0.852 AC: 9025 AN: 10594

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58043 AN: 68008

Other (OTH) AF: 0.867 AC: 1835 AN: 2116

Alfa AF: 0.863 Hom.: 46294

Bravo AF: 0.898

Asia WGS AF: 0.905 AC: 3143 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.8
DANN	Benign	0.40
PhyloP100		-0.012
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: rs1492099; hg19: chr3-148437503;