1-230714126-C-T

Variant names:

• chr1-230714126-C-T
• rs5051
• ENST00000680041.1:c.-196G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001382817.3(AGT):​c.-30-3273G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,032 control chromosomes in the GnomAD database, including 28,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (28493 hom., cov: 31)
  • Exomes 𝑓: 0.48 (23 hom.)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.48

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]

ENSG00000244137 (HGNC:58238):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-230714126-C-T is Benign according to our data. Variant chr1-230714126-C-T is described in ClinVar as [Benign]. Clinvar id is 296090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-230714126-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-3273G>A		intron_variant	Intron 1 of 4		NP_001369746.2
AGT	NM_001384479.1	c.-71G>A		upstream_gene_variant		ENST00000366667.6	NP_001371408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.-71G>A		upstream_gene_variant		1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88384 AN: 151728 Hom.: 28429 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.478 AC: 89 AN: 186 Hom.: 23 Cov.: 0 AF XY: 0.481 AC XY: 74 AN XY: 154

Gnomad4 AFR exome AF: 1.00

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.750

Gnomad4 NFE exome AF: 0.443

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.583 AC: 88505 AN: 151846 Hom.: 28493 Cov.: 31 AF XY: 0.587 AC XY: 43579 AN XY: 74194

Gnomad4 AFR AF: 0.843

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.831

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.566

Alfa AF: 0.447 Hom.: 15072

Bravo AF: 0.610

Asia WGS AF: 0.728 AC: 2530 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Renal tubular dysgenesis Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertension, essential, susceptibility to Benign:1

Dec 24, 2010

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.75
DANN	Benign	0.60
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs5051; hg19: chr1-230849872;