1-230710933-T-C

Position:

• chr1-230710933-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001384479.1(AGT):​c.-30-80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 1,517,660 control chromosomes in the GnomAD database, including 8,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (852 hom., cov: 32)
  • Exomes 𝑓: 0.094 (8066 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0110

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]

ENSG00000244137 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-230710933-T-C is Benign according to our data. Variant chr1-230710933-T-C is described in ClinVar as [Benign]. Clinvar id is 1247694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-30-80A>G		intron_variant		ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-80A>G		intron_variant			NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.-30-80A>G		intron_variant		1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13088 AN: 152170 Hom.: 854 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.0783

GnomAD4 exome AF: 0.0943 AC: 128724 AN: 1365372 Hom.: 8066 AF XY: 0.0940 AC XY: 64250 AN XY: 683284

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.212

Gnomad4 ASJ exome AF: 0.0336

Gnomad4 EAS exome AF: 0.339

Gnomad4 SAS exome AF: 0.0998

Gnomad4 FIN exome AF: 0.0544

Gnomad4 NFE exome AF: 0.0843

Gnomad4 OTH exome AF: 0.0953

GnomAD4 genome AF: 0.0860 AC: 13090 AN: 152288 Hom.: 852 Cov.: 32 AF XY: 0.0877 AC XY: 6531 AN XY: 74472

Gnomad4 AFR AF: 0.0474

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0357

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.111

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0841

Gnomad4 OTH AF: 0.0789

Alfa AF: 0.0865 Hom.: 1242

Bravo AF: 0.0943

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.50

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: rs11122576; hg19: chr1-230846679; COSMIC: COSV64185498;