rs2067853

Positions:

• chr1-230702512-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000680041.1(AGT):​c.*629C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 155,574 control chromosomes in the GnomAD database, including 5,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5642 hom., cov: 33)
  • Exomes 𝑓: 0.25 (134 hom.)
• Consequence: AGT ENST00000680041.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.487

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-230702512-G-A is Benign according to our data. Variant chr1-230702512-G-A is described in ClinVar as [Benign]. Clinvar id is 368868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1			downstream_gene_variant		ENST00000366667.6
AGT	NM_001382817.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6			downstream_gene_variant		1	NM_001384479.1	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38199 AN: 152034 Hom.: 5648 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.250 AC: 857 AN: 3422 Hom.: 134 Cov.: 0 AF XY: 0.247 AC XY: 427 AN XY: 1726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.141

Gnomad4 ASJ exome AF: 0.833

Gnomad4 EAS exome AF: 0.0854

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.375

Gnomad4 NFE exome AF: 0.307

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.251 AC: 38191 AN: 152152 Hom.: 5642 Cov.: 33 AF XY: 0.252 AC XY: 18735 AN XY: 74384

Gnomad4 AFR AF: 0.107

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.328

Gnomad4 OTH AF: 0.261

Alfa AF: 0.296 Hom.: 7048

Bravo AF: 0.230

Asia WGS AF: 0.197 AC: 690 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal tubular dysgenesis Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2067853; hg19: chr1-230838258;