rs7536290

Variant names:

• chr1-230700956-A-G
• rs7536290
• ENST00000680783.1:c.830-6517T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-230700956-A-G
• chr1-230700956-A-T

Variant summary

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

The ENST00000680783.1(AGT):​c.830-6517T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,034 control chromosomes in the GnomAD database, including 4,900 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 0.24 (4900 hom., cov: 31)
• Consequence: AGT ENST00000680783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.598
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000680783.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000680783.1		c.830-6517T>C		intron	N/A	ENSP00000506329.1	A0A7P0TAP4
	AGT	ENST00000679738.1		n.*786+1399T>C		intron	N/A	ENSP00000505063.1	P01019
	AGT	ENST00000679802.1		n.*1676+1399T>C		intron	N/A	ENSP00000505184.1	A0A7P0Z441

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36218 AN: 151914 Hom.: 4884 Cov.: 31

Gnomad AFR AF: 0.363

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.250

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.239 AC: 36261 AN: 152034 Hom.: 4900 Cov.: 31 AF XY: 0.242 AC XY: 17976 AN XY: 74328

African (AFR) AF: 0.362 AC: 15011 AN: 41436

American (AMR) AF: 0.264 AC: 4042 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 549 AN: 3468

East Asian (EAS) AF: 0.249 AC: 1288 AN: 5174

South Asian (SAS) AF: 0.213 AC: 1027 AN: 4812

European-Finnish (FIN) AF: 0.257 AC: 2713 AN: 10560

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10789 AN: 67984

Other (OTH) AF: 0.228 AC: 481 AN: 2114

Alfa AF: 0.185 Hom.: 5428

Bravo AF: 0.250

Asia WGS AF: 0.243 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		0.60

Splicing

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

Other links and lift over

dbSNP: rs7536290; hg19: chr1-230836702;