rs2493134

Positions:

• chr1-230713613-T-C

Variant summary

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

The NM_001384479.1(AGT):​c.-31+473A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,018 control chromosomes in the GnomAD database, including 27,530 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 0.57 (27530 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.811 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1	c.-31+473A>G		intron_variant		ENST00000366667.6
AGT	NM_001382817.3	c.-30-2760A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6	c.-31+473A>G		intron_variant		1	NM_001384479.1	P1
	ENST00000412344.1	n.381-2760A>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.574 AC: 87187 AN: 151900 Hom.: 27477 Cov.: 32

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.431

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.420

Gnomad OTH AF: 0.548

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

GnomAD4 genome AF: 0.574 AC: 87298 AN: 152018 Hom.: 27530 Cov.: 32 AF XY: 0.579 AC XY: 43051 AN XY: 74312

Gnomad4 AFR AF: 0.817

Gnomad4 AMR AF: 0.631

Gnomad4 ASJ AF: 0.431

Gnomad4 EAS AF: 0.832

Gnomad4 SAS AF: 0.620

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.420

Gnomad4 OTH AF: 0.552

Alfa AF: 0.459 Hom.: 22814

Bravo AF: 0.600

Asia WGS AF: 0.728 AC: 2528 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.47
DANN	Benign	0.24

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: rs2493134; hg19: chr1-230849359;