rs7079

chr1-230702585-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384479.1(AGT):c.*556C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 157,228 control chromosomes in the GnomAD database, including 5,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5642 hom., cov: 33)
  • Exomes 𝑓: 0.26 (216 hom.)
• Consequence: AGT NM_001384479.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0350

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-230702585-G-T is Benign according to our data. Variant chr1-230702585-G-T is described in ClinVar as [Benign]. Clinvar id is 296063.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1	c.*556C>A		3_prime_UTR_variant	5/5	ENST00000366667.6
AGT	NM_001382817.3	c.*556C>A		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6	c.*556C>A		3_prime_UTR_variant	5/5	1	NM_001384479.1	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38192 AN: 151958 Hom.: 5648 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.261 AC: 1344 AN: 5152 Hom.: 216 Cov.: 0 AF XY: 0.250 AC XY: 653 AN XY: 2608

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.375

Gnomad4 EAS exome AF: 0.0776

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.325

Gnomad4 OTH exome AF: 0.304

GnomAD4 genome AF: 0.251 AC: 38184 AN: 152076 Hom.: 5642 Cov.: 33 AF XY: 0.252 AC XY: 18731 AN XY: 74332

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.296

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.260

Alfa AF: 0.311 Hom.: 10838

Bravo AF: 0.230

Asia WGS AF: 0.197 AC: 690 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal tubular dysgenesis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	1.7
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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

Other links and lift over

dbSNP: rs7079; hg19: chr1-230838331;