rs2006765

Variant names:

• chr1-230697920-G-A
• rs2006765
• ENST00000680783.1:c.830-3481C>T

Variant summary

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

The ENST00000680783.1(AGT):​c.830-3481C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,104 control chromosomes in the GnomAD database, including 16,100 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 0.42 (16100 hom., cov: 33)
• Consequence: AGT ENST00000680783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000680783.1	c.830-3481C>T		intron_variant	Intron 2 of 2			ENSP00000506329.1
AGT	ENST00000679738.1	n.*787-1081C>T		intron_variant	Intron 5 of 6			ENSP00000505063.1
AGT	ENST00000679802.1	n.*1677-1081C>T		intron_variant	Intron 6 of 7			ENSP00000505184.1

Frequencies

GnomAD3 genomes AF: 0.417 AC: 63340 AN: 151988 Hom.: 16104 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.582

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.416 AC: 63333 AN: 152104 Hom.: 16100 Cov.: 33 AF XY: 0.411 AC XY: 30570 AN XY: 74354

African (AFR) AF: 0.153 AC: 6369 AN: 41504

American (AMR) AF: 0.344 AC: 5262 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.582 AC: 2017 AN: 3468

East Asian (EAS) AF: 0.164 AC: 846 AN: 5166

South Asian (SAS) AF: 0.374 AC: 1803 AN: 4820

European-Finnish (FIN) AF: 0.561 AC: 5926 AN: 10568

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39583 AN: 67986

Other (OTH) AF: 0.434 AC: 914 AN: 2104

Alfa AF: 0.432 Hom.: 2366

Bravo AF: 0.387

Asia WGS AF: 0.262 AC: 915 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.24
DANN	Benign	0.28
PhyloP100		-1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2006765; hg19: chr1-230833666;