1-230704350-T-C

Variant names:

• chr1-230704350-T-C
• rs1926723
• NM_001384479.1:c.1098-13A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001384479.1(AGT):​c.1098-13A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0878 in 1,613,506 control chromosomes in the GnomAD database, including 8,470 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.080 (795 hom., cov: 33)
  • Exomes 𝑓: 0.089 (7675 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -4.98
• Publications: 25 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 1-230704350-T-C is Benign according to our data. Variant chr1-230704350-T-C is described in ClinVar as Benign. ClinVar VariationId is 296076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001384479.1	MANE Select	c.1098-13A>G		intron	N/A	NP_001371408.1
	AGT	NM_001382817.3		c.1098-13A>G		intron	N/A	NP_001369746.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.1098-13A>G		intron	N/A	ENSP00000355627.5
	AGT	ENST00000681347.1		n.3191A>G		non_coding_transcript_exon	Exon 3 of 6
	AGT	ENST00000680041.1		c.1098-13A>G		intron	N/A	ENSP00000504866.1

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12249 AN: 152122 Hom.: 795 Cov.: 33

Gnomad AFR AF: 0.0412

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0799

Gnomad OTH AF: 0.0728

GnomAD2 exomes AF: 0.112 AC: 28057 AN: 250038 AF XY: 0.107

Gnomad AFR exome AF: 0.0416

Gnomad AMR exome AF: 0.212

Gnomad ASJ exome AF: 0.0313

Gnomad EAS exome AF: 0.351

Gnomad FIN exome AF: 0.0519

Gnomad NFE exome AF: 0.0787

Gnomad OTH exome AF: 0.0862

GnomAD4 exome AF: 0.0886 AC: 129475 AN: 1461266 Hom.: 7675 Cov.: 32 AF XY: 0.0884 AC XY: 64281 AN XY: 726916

African (AFR) AF: 0.0392 AC: 1312 AN: 33476

American (AMR) AF: 0.205 AC: 9144 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.0322 AC: 842 AN: 26130

East Asian (EAS) AF: 0.329 AC: 13037 AN: 39686

South Asian (SAS) AF: 0.0955 AC: 8227 AN: 86172

European-Finnish (FIN) AF: 0.0534 AC: 2851 AN: 53384

Middle Eastern (MID) AF: 0.0406 AC: 233 AN: 5732

European-Non Finnish (NFE) AF: 0.0795 AC: 88370 AN: 1111712

Other (OTH) AF: 0.0904 AC: 5459 AN: 60370

GnomAD4 genome AF: 0.0805 AC: 12255 AN: 152240 Hom.: 795 Cov.: 33 AF XY: 0.0818 AC XY: 6089 AN XY: 74428

African (AFR) AF: 0.0412 AC: 1713 AN: 41558

American (AMR) AF: 0.136 AC: 2073 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1792 AN: 5152

South Asian (SAS) AF: 0.106 AC: 510 AN: 4828

European-Finnish (FIN) AF: 0.0423 AC: 449 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5433 AN: 68008

Other (OTH) AF: 0.0754 AC: 159 AN: 2110

Alfa AF: 0.0655 Hom.: 222

Bravo AF: 0.0881

Asia WGS AF: 0.223 AC: 775 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jun 09, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Renal tubular dysgenesis Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.0060
DANN	Benign	0.36
PhyloP100		-5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1926723; hg19: chr1-230840096; COSMIC: COSV64184131;