rs3827749

chr1-230705813-G-A

Variant summary

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

The NM_001384479.1(AGT):c.1097+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,347,132 control chromosomes in the GnomAD database, including 36,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.29 (7050 hom., cov: 33)
  • Exomes 𝑓: 0.21 (29770 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.87

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=-0.92).
• BP6: Variant 1-230705813-G-A is Benign according to our data. Variant chr1-230705813-G-A is described in ClinVar as [Benign]. Clinvar id is 1276076.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1	c.1097+120C>T		intron_variant		ENST00000366667.6
AGT	NM_001382817.3	c.1097+120C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6	c.1097+120C>T		intron_variant		1	NM_001384479.1	P1

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43488 AN: 151926 Hom.: 7024 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.211 AC: 252597 AN: 1195088 Hom.: 29770 AF XY: 0.211 AC XY: 126925 AN XY: 600386

Gnomad4 AFR exome AF: 0.447

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.185

Gnomad4 EAS exome AF: 0.321

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.254

Gnomad4 NFE exome AF: 0.183

Gnomad4 OTH exome AF: 0.226

GnomAD4 genome AF: 0.286 AC: 43555 AN: 152044 Hom.: 7050 Cov.: 33 AF XY: 0.291 AC XY: 21640 AN XY: 74292

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.283

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.292

Alfa AF: 0.256 Hom.: 693

Bravo AF: 0.301

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.0070
Dann	Benign	0.33
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3827749; hg19: chr1-230841559; COSMIC: COSV64184823; COSMIC: COSV64184823;