1-230727252-C-T

Variant names:

• chr1-230727252-C-T
• rs1326889
• NM_001382817.3:c.-30-16399G>A

Variant summary

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

The NM_001382817.3(AGT):​c.-30-16399G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.656 in 152,052 control chromosomes in the GnomAD database, including 35,098 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 0.66 (35098 hom., cov: 32)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672
• Publications: 11 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)

ENSG00000244137 (HGNC:58238):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-16399G>A		intron_variant	Intron 1 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000681269.1	c.-30-16399G>A		intron_variant	Intron 1 of 4			ENSP00000505985.1
ENSG00000244137	ENST00000412344.1	n.381-16399G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99563 AN: 151934 Hom.: 35033 Cov.: 32

Gnomad AFR AF: 0.894

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.908

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.500

Gnomad OTH AF: 0.629

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

GnomAD4 genome AF: 0.656 AC: 99688 AN: 152052 Hom.: 35098 Cov.: 32 AF XY: 0.662 AC XY: 49213 AN XY: 74310

African (AFR) AF: 0.895 AC: 37145 AN: 41512

American (AMR) AF: 0.697 AC: 10641 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1962 AN: 3468

East Asian (EAS) AF: 0.907 AC: 4683 AN: 5162

South Asian (SAS) AF: 0.764 AC: 3683 AN: 4818

European-Finnish (FIN) AF: 0.524 AC: 5524 AN: 10550

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.500 AC: 33999 AN: 67946

Other (OTH) AF: 0.633 AC: 1339 AN: 2116

Alfa AF: 0.551 Hom.: 30540

Bravo AF: 0.677

Asia WGS AF: 0.831 AC: 2889 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.82
DANN	Benign	0.24
PhyloP100		-0.67

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1326889; hg19: chr1-230862998;