rs12721274
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_000685.5(AGTR1):c.*556T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000453 in 216,178 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00062 ( 3 hom., cov: 33)
Exomes 𝑓: 0.000047 ( 0 hom. )
Consequence
AGTR1
NM_000685.5 3_prime_UTR
NM_000685.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.0250
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000624 (95/152320) while in subpopulation AFR AF= 0.000625 (26/41576). AF 95% confidence interval is 0.000438. There are 3 homozygotes in gnomad4. There are 44 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
?
High Homozygotes in GnomAd4 at 3 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGTR1 | NM_000685.5 | c.*556T>C | 3_prime_UTR_variant | 3/3 | ENST00000349243.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGTR1 | ENST00000349243.8 | c.*556T>C | 3_prime_UTR_variant | 3/3 | 1 | NM_000685.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000624 AC: 95AN: 152202Hom.: 3 Cov.: 33
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GnomAD4 exome AF: 0.0000470 AC: 3AN: 63858Hom.: 0 Cov.: 0 AF XY: 0.0000309 AC XY: 1AN XY: 32342
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GnomAD4 genome ? AF: 0.000624 AC: 95AN: 152320Hom.: 3 Cov.: 33 AF XY: 0.000591 AC XY: 44AN XY: 74488
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Renal tubular dysgenesis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at