Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_000685.5(AGTR1):c.*135C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00301 in 1,257,812 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 56 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 34 hom. )

Consequence

AGTR1
NM_000685.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.701

Publications

7 publications found

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]

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)

AGTR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 3-148742250-C-T is Benign according to our data. Variant chr3-148742250-C-T is described in ClinVar as Benign. ClinVar VariationId is 343678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0134 (2046/152312) while in subpopulation AFR AF = 0.0444 (1844/41562). AF 95% confidence interval is 0.0427. There are 56 homozygotes in GnomAd4. There are 958 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 56 AR,Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000685.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AGTR1	NM_000685.5	MANE Select	c.*135C>T	3_prime_UTR	Exon 3 of 3	NP_000676.1
AGTR1	NM_001382736.1		c.*135C>T	3_prime_UTR	Exon 2 of 2	NP_001369665.1
AGTR1	NM_001382737.1		c.*135C>T	3_prime_UTR	Exon 3 of 3	NP_001369666.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
AGTR1	ENST00000349243.8	TSL:1 MANE Select	c.*135C>T	3_prime_UTR	Exon 3 of 3	ENSP00000273430.3
AGTR1	ENST00000404754.2	TSL:1	c.*135C>T	3_prime_UTR	Exon 2 of 2	ENSP00000385612.2
AGTR1	ENST00000497524.5	TSL:1	c.*135C>T	3_prime_UTR	Exon 2 of 2	ENSP00000419422.1

Frequencies

GnomAD3 genomes

AF:

0.0134

AC:

2037

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0443

Gnomad AMI

AF:

0.0615

Gnomad AMR

AF:

0.00609

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000659

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00331

AC:

809

AN:

244568

AF XY:

0.00262

show subpopulations

Gnomad AFR exome

AF:

0.0456

Gnomad AMR exome

AF:

0.00242

Gnomad ASJ exome

AF:

0.000201

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000605

Gnomad NFE exome

AF:

0.000273

Gnomad OTH exome

AF:

0.00285

GnomAD4 exome

AF:

0.00157

AC:

1741

AN:

1105500

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

793

AN XY:

566056

show subpopulations

African (AFR)

AF:

0.0463

AC:

1208

AN:

26116

American (AMR)

AF:

0.00274

AC:

121

AN:

44138

Ashkenazi Jewish (ASJ)

AF:

0.000167

AC:

AN:

23950

East Asian (EAS)

AF:

0.00

AC:

AN:

38016

South Asian (SAS)

AF:

0.0000638

AC:

AN:

78364

European-Finnish (FIN)

AF:

0.000701

AC:

AN:

52808

Middle Eastern (MID)

AF:

0.00450

AC:

AN:

5114

European-Non Finnish (NFE)

AF:

0.000207

AC:

163

AN:

788370

Other (OTH)

AF:

0.00370

AC:

180

AN:

48624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

176

263

351

439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

114

152

190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0134

AC:

2046

AN:

152312

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

958

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.0444

AC:

1844

AN:

41562

American (AMR)

AF:

0.00608

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68030

Other (OTH)

AF:

0.0109

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

196

294

392

490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00882

Hom.:

Bravo

AF:

0.0151

Asia WGS

AF:

0.00606

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Renal tubular dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.36

(source)

DANN

Benign

0.50

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over