rs7536290

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000680783.1	c.830-6517T>C		intron_variant				ENSP00000506329
AGT	ENST00000679738.1	c.*786+1399T>C		intron_variant, NMD_transcript_variant				ENSP00000505063
AGT	ENST00000679802.1	c.*1676+1399T>C		intron_variant, NMD_transcript_variant				ENSP00000505184

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

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.158

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.228

Alfa AF: 0.176 Hom.: 3499

Bravo AF: 0.250

Asia WGS AF: 0.243 AC: 845 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7536290; hg19: chr1-230836702;