rs7549009

Variant names:

• chr1-230719325-G-A
• rs7549009
• NM_001382817.3:c.-30-8472C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-230719325-G-A
• chr1-230719325-G-T

Variant summary

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

The NM_001382817.3(AGT):​c.-30-8472C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,576 control chromosomes in the GnomAD database, including 4,129 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 0.20 (4129 hom., cov: 31)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 5 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001382817.3		c.-30-8472C>T		intron	N/A	NP_001369746.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000681269.1		c.-30-8472C>T		intron	N/A	ENSP00000505985.1
	ENSG00000244137	ENST00000412344.1	TSL:3	n.381-8472C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.198 AC: 29981 AN: 151476 Hom.: 4107 Cov.: 31

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.198 AC: 30060 AN: 151576 Hom.: 4129 Cov.: 31 AF XY: 0.200 AC XY: 14826 AN XY: 74060

African (AFR) AF: 0.329 AC: 13570 AN: 41250

American (AMR) AF: 0.279 AC: 4247 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2520 AN: 5146

South Asian (SAS) AF: 0.210 AC: 1008 AN: 4794

European-Finnish (FIN) AF: 0.0885 AC: 927 AN: 10470

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7080 AN: 67920

Other (OTH) AF: 0.191 AC: 400 AN: 2098

Alfa AF: 0.139 Hom.: 7906

Bravo AF: 0.224

Asia WGS AF: 0.364 AC: 1266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.43
DANN	Benign	0.49
PhyloP100		-0.37

Splicing

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

Other links and lift over

dbSNP: rs7549009; hg19: chr1-230855071;