chr3-148741019-C-T

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

Scores

10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.645
Variant links:
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
AGTR1NM_000685.5 linkuse as main transcriptc.-17C>T 5_prime_UTR_variant 3/3 ENST00000349243.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
AGTR1ENST00000349243.8 linkuse as main transcriptc.-17C>T 5_prime_UTR_variant 3/31 NM_000685.5 P1

Frequencies

GnomAD3 genomes
AF:
0.000131
AC:
20
AN:
152114
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000235
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000148
AC:
37
AN:
250130
Hom.:
0
AF XY:
0.000125
AC XY:
17
AN XY:
135508
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000212
Gnomad OTH exome
AF:
0.000329
GnomAD4 exome
AF:
0.000235
AC:
343
AN:
1461218
Hom.:
2
Cov.:
31
AF XY:
0.000243
AC XY:
177
AN XY:
726914
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000928
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000279
Gnomad4 OTH exome
AF:
0.000182
GnomAD4 genome
AF:
0.000131
AC:
20
AN:
152114
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74280
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000235
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000108
Hom.:
0
Bravo
AF:
0.000128
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.000165
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 submitterclinical testingPreventionGenetics, part of Exact SciencesNov 03, 2022The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.37
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
12
DANN
Benign
0.86
DEOGEN2
Benign
0.27
T;T
FATHMM_MKL
Benign
0.34
N
LIST_S2
Benign
0.65
T;T
MetaRNN
Benign
0.13
T;T
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D
PrimateAI
Benign
0.28
T
Sift4G
Benign
0.43
T;T
Vest4
0.069
MVP
0.74
GERP RS
3.0
gMVP
0.21

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs376789057; hg19: chr3-148458806; API