1-230707700-G-A

Position:

• chr1-230707700-G-A

Variant summary

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

The NM_001384479.1(AGT):​c.830-1500C>T 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 152,024 control chromosomes in the GnomAD database, including 5,570 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 (5570 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001384479.1	c.830-1500C>T		intron_variant		ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.830-1500C>T		intron_variant			NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.830-1500C>T		intron_variant		1	NM_001384479.1	ENSP00000355627	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39689 AN: 151906 Hom.: 5550 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.191

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.261 AC: 39752 AN: 152024 Hom.: 5570 Cov.: 32 AF XY: 0.267 AC XY: 19862 AN XY: 74336

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.191

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.270

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.274

Alfa AF: 0.220 Hom.: 808

Bravo AF: 0.273

Asia WGS AF: 0.286 AC: 992 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.70

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: rs3789667; hg19: chr1-230843446;