1-230708054-G-T

Variant names:

• chr1-230708054-G-T
• rs3789671
• NM_001384479.1:c.830-1854C>A

Variant summary

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

The NM_001384479.1(AGT):​c.830-1854C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 152,032 control chromosomes in the GnomAD database, including 5,897 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 0.26 (5897 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.720
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.830-1854C>A		intron_variant	Intron 2 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.830-1854C>A		intron_variant	Intron 2 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.830-1854C>A		intron_variant	Intron 2 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39603 AN: 151912 Hom.: 5878 Cov.: 32

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.322

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.261 AC: 39658 AN: 152032 Hom.: 5897 Cov.: 32 AF XY: 0.261 AC XY: 19426 AN XY: 74334

African (AFR) AF: 0.372 AC: 15401 AN: 41410

American (AMR) AF: 0.277 AC: 4230 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 432 AN: 3464

East Asian (EAS) AF: 0.532 AC: 2744 AN: 5158

South Asian (SAS) AF: 0.322 AC: 1549 AN: 4816

European-Finnish (FIN) AF: 0.135 AC: 1430 AN: 10592

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.195 AC: 13239 AN: 67982

Other (OTH) AF: 0.225 AC: 475 AN: 2114

Alfa AF: 0.197 Hom.: 1278

Bravo AF: 0.275

Asia WGS AF: 0.411 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.20
DANN	Benign	0.52
PhyloP100		-0.72
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3789671; hg19: chr1-230843800;