1-230707811-T-C

Variant names:

• chr1-230707811-T-C
• rs2493132
• NM_001384479.1:c.830-1611A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384479.1(AGT):​c.830-1611A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 152,034 control chromosomes in the GnomAD database, including 13,083 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 0.40 (13083 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23
• Publications: 20 publications found

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]

AGT Gene-Disease associations (from GenCC):

• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.830-1611A>G		intron_variant	Intron 2 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.830-1611A>G		intron_variant	Intron 2 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.830-1611A>G		intron_variant	Intron 2 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60784 AN: 151914 Hom.: 13060 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.372

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.400 AC: 60862 AN: 152034 Hom.: 13083 Cov.: 32 AF XY: 0.407 AC XY: 30208 AN XY: 74310

African (AFR) AF: 0.507 AC: 21001 AN: 41450

American (AMR) AF: 0.515 AC: 7873 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3470

East Asian (EAS) AF: 0.664 AC: 3426 AN: 5156

South Asian (SAS) AF: 0.404 AC: 1946 AN: 4816

European-Finnish (FIN) AF: 0.354 AC: 3746 AN: 10570

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.301 AC: 20429 AN: 67976

Other (OTH) AF: 0.407 AC: 860 AN: 2112

Alfa AF: 0.331 Hom.: 5365

Bravo AF: 0.423

Asia WGS AF: 0.549 AC: 1905 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	0.33
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2493132; hg19: chr1-230843557;