chr3-148741019-C-T
Position:
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2
The NM_000685.5(AGTR1):c.-17C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000225 in 1,613,332 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00023 ( 2 hom. )
Consequence
AGTR1
NM_000685.5 5_prime_UTR
NM_000685.5 5_prime_UTR
Scores
10
Clinical Significance
Conservation
PhyloP100: 0.645
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.12826163).
BS1
Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.000235 (343/1461218) while in subpopulation MID AF= 0.00052 (3/5768). AF 95% confidence interval is 0.000253. There are 2 homozygotes in gnomad4_exome. There are 177 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AGTR1 | NM_000685.5 | c.-17C>T | 5_prime_UTR_variant | 3/3 | ENST00000349243.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AGTR1 | ENST00000349243.8 | c.-17C>T | 5_prime_UTR_variant | 3/3 | 1 | NM_000685.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152114Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
20
AN:
152114
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000148 AC: 37AN: 250130Hom.: 0 AF XY: 0.000125 AC XY: 17AN XY: 135508
GnomAD3 exomes
AF:
AC:
37
AN:
250130
Hom.:
AF XY:
AC XY:
17
AN XY:
135508
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000235 AC: 343AN: 1461218Hom.: 2 Cov.: 31 AF XY: 0.000243 AC XY: 177AN XY: 726914
GnomAD4 exome
AF:
AC:
343
AN:
1461218
Hom.:
Cov.:
31
AF XY:
AC XY:
177
AN XY:
726914
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.000131 AC: 20AN: 152114Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74280
GnomAD4 genome
AF:
AC:
20
AN:
152114
Hom.:
Cov.:
33
AF XY:
AC XY:
11
AN XY:
74280
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
0
ESP6500EA
AF:
AC:
1
ExAC
AF:
AC:
20
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
AGTR1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 03, 2022 | The AGTR1 c.71C>T variant is predicted to result in the amino acid substitution p.Ser24Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.019% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/3-148458806-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D
PrimateAI
Benign
T
Sift4G
Benign
T;T
Vest4
MVP
GERP RS
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at