1-230708450-C-G

Variant names:

• chr1-230708450-C-G
• rs2478544
• NM_001384479.1:c.829+1545G>C

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+1545G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,082 control chromosomes in the GnomAD database, including 6,357 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 0.27 (6357 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• Publications: 13 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.829+1545G>C		intron_variant	Intron 2 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.829+1545G>C		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+1545G>C		intron_variant	Intron 2 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40977 AN: 151964 Hom.: 6344 Cov.: 32

Gnomad AFR AF: 0.427

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.279

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.263

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

GnomAD4 genome AF: 0.270 AC: 41029 AN: 152082 Hom.: 6357 Cov.: 32 AF XY: 0.273 AC XY: 20324 AN XY: 74336

African (AFR) AF: 0.427 AC: 17689 AN: 41458

American (AMR) AF: 0.277 AC: 4236 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.279 AC: 968 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5162

South Asian (SAS) AF: 0.245 AC: 1182 AN: 4818

European-Finnish (FIN) AF: 0.272 AC: 2876 AN: 10574

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11884 AN: 67998

Other (OTH) AF: 0.270 AC: 570 AN: 2114

Alfa AF: 0.108 Hom.: 155

Bravo AF: 0.280

Asia WGS AF: 0.259 AC: 900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.60
PhyloP100		-0.28
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: rs2478544; hg19: chr1-230844196;