1-230708564-T-C

Variant names:

• chr1-230708564-T-C
• rs2478543
• NM_001384479.1:c.829+1431A>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.829+1431A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.577 in 151,884 control chromosomes in the GnomAD database, including 27,789 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 0.58 (27789 hom., cov: 31)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0310
• Publications: 15 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.829+1431A>G		intron_variant	Intron 2 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.829+1431A>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.829+1431A>G		intron_variant	Intron 2 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87518 AN: 151766 Hom.: 27735 Cov.: 31

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.835

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.577 AC: 87631 AN: 151884 Hom.: 27789 Cov.: 31 AF XY: 0.582 AC XY: 43197 AN XY: 74224

African (AFR) AF: 0.825 AC: 34175 AN: 41426

American (AMR) AF: 0.631 AC: 9648 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1524 AN: 3468

East Asian (EAS) AF: 0.834 AC: 4277 AN: 5126

South Asian (SAS) AF: 0.617 AC: 2962 AN: 4802

European-Finnish (FIN) AF: 0.446 AC: 4706 AN: 10548

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.422 AC: 28631 AN: 67920

Other (OTH) AF: 0.554 AC: 1166 AN: 2106

Alfa AF: 0.561 Hom.: 3725

Bravo AF: 0.603

Asia WGS AF: 0.716 AC: 2487 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.49
PhyloP100		-0.031
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: rs2478543; hg19: chr1-230844310;