Genetic Variant NM_001384479.1:c.-31+33T>C (chr1-230714053-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001384479.1(AGT):c.-31+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,938 control chromosomes in the GnomAD database, including 28,063 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 0.58 ( 28057 hom., cov: 31)

Exomes 𝑓: 0.57 ( 6 hom. )

Consequence

AGT
NM_001384479.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

26 publications found

Variant links:

Genes affected

AGT (HGNC:333): (angiotensinogen) The protein encoded by this gene, pre-angiotensinogen or angiotensinogen precursor, is expressed in the liver and is cleaved by the enzyme renin in response to lowered blood pressure. The resulting product, angiotensin I, is then cleaved by angiotensin converting enzyme (ACE) to generate the physiologically active enzyme angiotensin II. The protein is involved in maintaining blood pressure, body fluid and electrolyte homeostasis, and in the pathogenesis of essential hypertension and preeclampsia. Mutations in this gene are associated with susceptibility to essential hypertension, and can cause renal tubular dysgenesis, a severe disorder of renal tubular development. Defects in this gene have also been associated with non-familial structural atrial fibrillation, and inflammatory bowel disease. [provided by RefSeq, Nov 2019]

AGT Gene-Disease associations (from GenCC):

renal tubular dysgenesis of genetic origin
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

AGT links:

ENSG00000244137 (HGNC:58238):

ENSG00000244137 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1 link	c.-31+33T>C		intron_variant	Intron 1 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3 link	c.-30-3200T>C		intron_variant	Intron 1 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6 link	c.-31+33T>C		intron_variant	Intron 1 of 4	1	NM_001384479.1	ENSP00000355627.5		P01019

Frequencies

GnomAD3 genomes

AF:

0.579

AC:

87899

AN:

151778

Hom.:

28002

Cov.:

show subpopulations

Gnomad AFR

AF:

0.829

Gnomad AMI

AF:

0.432

Gnomad AMR

AF:

0.639

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.833

Gnomad SAS

AF:

0.624

Gnomad FIN

AF:

0.444

Gnomad MID

AF:

0.516

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.562

GnomAD4 exome

AF:

0.575

AC:

AN:

Hom.:

Cov.:

AF XY:

0.625

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.575

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.579

AC:

88011

AN:

151898

Hom.:

28057

Cov.:

AF XY:

0.584

AC XY:

43337

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.830

AC:

34396

AN:

41460

American (AMR)

AF:

0.640

AC:

9768

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1559

AN:

3464

East Asian (EAS)

AF:

0.833

AC:

4275

AN:

5134

South Asian (SAS)

AF:

0.622

AC:

2995

AN:

4812

European-Finnish (FIN)

AF:

0.444

AC:

4684

AN:

10538

Middle Eastern (MID)

AF:

0.493

AC:

145

AN:

294

European-Non Finnish (NFE)

AF:

0.421

AC:

28599

AN:

67906

Other (OTH)

AF:

0.566

AC:

1196

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

1674

3348

5021

6695

8369

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

718

1436

2154

2872

3590

<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:

0.479

Hom.:

24096

Bravo

AF:

0.606

Asia WGS

AF:

0.727

AC:

2527

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.4

(source)

DANN

Benign

0.42

PhyloP100

-0.058

PromoterAI

0.063

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Mutation Taster

=100/0

polymorphism (auto)

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over