rs3789669

Positions:

• chr1-230707887-A-G
• chr1-230707887-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384479.1(AGT):​c.830-1687T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,022 control chromosomes in the GnomAD database, including 5,918 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 (5918 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001384479.1	c.830-1687T>C		intron_variant		ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.830-1687T>C		intron_variant			NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.830-1687T>C		intron_variant		1	NM_001384479.1	ENSP00000355627	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39710 AN: 151904 Hom.: 5900 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.533

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.195

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.262 AC: 39766 AN: 152022 Hom.: 5918 Cov.: 32 AF XY: 0.262 AC XY: 19458 AN XY: 74310

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.533

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.134

Gnomad4 NFE AF: 0.195

Gnomad4 OTH AF: 0.223

Alfa AF: 0.147 Hom.: 389

Bravo AF: 0.276

Asia WGS AF: 0.414 AC: 1439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.53
DANN	Benign	0.31
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: rs3789669; hg19: chr1-230843633;