Genetic Variant AGT:c.-210A>C (chr1-230714140-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001382817.3(AGT):c.-30-3287A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,786 control chromosomes in the GnomAD database, including 2,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2240 hom., cov: 31)

Exomes 𝑓: 0.20 ( 6 hom. )

Consequence

AGT
NM_001382817.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.202

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 links:

ENSG00000244137 (HGNC:58238):

ENSG00000244137 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 1-230714140-T-G is Benign according to our data. Variant chr1-230714140-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 296092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-230714140-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3 link	c.-30-3287A>C		intron_variant	Intron 1 of 4		NP_001369746.2
AGT	NM_001384479.1 link	c.-85A>C		upstream_gene_variant		ENST00000366667.6	NP_001371408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6 link	c.-85A>C		upstream_gene_variant		1	NM_001384479.1	ENSP00000355627.5		P01019

Frequencies

GnomAD3 genomes

AF:

0.169

AC:

25626

AN:

151492

Hom.:

2239

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.282

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.184

Gnomad FIN

AF:

0.216

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.177

GnomAD4 exome

AF:

0.198

AC:

AN:

172

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

140

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.250

Gnomad4 EAS exome

AF:

0.167

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.167

GnomAD4 genome

AF:

0.169

AC:

25633

AN:

151614

Hom.:

2240

Cov.:

AF XY:

0.171

AC XY:

12679

AN XY:

74062

show subpopulations

Gnomad4 AFR

AF:

0.147

Gnomad4 AMR

AF:

0.186

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.168

Gnomad4 SAS

AF:

0.182

Gnomad4 FIN

AF:

0.216

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.123

Hom.:

332

Bravo

AF:

0.166

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 18, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30383794, 9403548, 22216295, 9931090, 19021695, 18802024) -

Renal tubular dysgenesis

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.6

DANN

Benign

0.74

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over