rs943580

Positions:

• chr1-230701298-G-A
• chr1-230701298-G-C

Variant summary

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

The ENST00000680783.1(AGT):​c.830-6859C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,910 control chromosomes in the GnomAD database, including 16,256 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 (16256 hom., cov: 31)
• Consequence: AGT ENST00000680783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.230701298G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000680783.1	c.830-6859C>T		intron_variant				ENSP00000506329.1
AGT	ENST00000679738.1	n.*786+1057C>T		intron_variant				ENSP00000505063.1
AGT	ENST00000679802.1	n.*1676+1057C>T		intron_variant				ENSP00000505184.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63684 AN: 151792 Hom.: 16259 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.419 AC: 63681 AN: 151910 Hom.: 16256 Cov.: 31 AF XY: 0.414 AC XY: 30716 AN XY: 74208

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.158

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.560

Gnomad4 NFE AF: 0.585

Gnomad4 OTH AF: 0.442

Alfa AF: 0.517 Hom.: 13642

Bravo AF: 0.390

Asia WGS AF: 0.261 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs943580; hg19: chr1-230837044;