rs2493134

Variant names:

• chr1-230713613-T-C
• rs2493134
• NM_001384479.1:c.-31+473A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384479.1(AGT):​c.-31+473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,018 control chromosomes in the GnomAD database, including 27,530 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 0.57 (27530 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 32 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)

ENSG00000244137 (HGNC:58238):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-31+473A>G		intron_variant	Intron 1 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-2760A>G		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	c.-31+473A>G		intron_variant	Intron 1 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87187 AN: 151900 Hom.: 27477 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.548

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.574 AC: 87298 AN: 152018 Hom.: 27530 Cov.: 32 AF XY: 0.579 AC XY: 43051 AN XY: 74312

African (AFR) AF: 0.817 AC: 33923 AN: 41502

American (AMR) AF: 0.631 AC: 9639 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 1494 AN: 3464

East Asian (EAS) AF: 0.832 AC: 4296 AN: 5164

South Asian (SAS) AF: 0.620 AC: 2988 AN: 4816

European-Finnish (FIN) AF: 0.445 AC: 4698 AN: 10564

Middle Eastern (MID) AF: 0.497 AC: 146 AN: 294

European-Non Finnish (NFE) AF: 0.420 AC: 28551 AN: 67926

Other (OTH) AF: 0.552 AC: 1169 AN: 2116

Alfa AF: 0.471 Hom.: 30454

Bravo AF: 0.600

Asia WGS AF: 0.728 AC: 2528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.24
PhyloP100		-1.2
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: rs2493134; hg19: chr1-230849359;