1-230702565-AG-A

Position:

• chr1-230702565-AG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001384479.1(AGT):​c.*575del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0117 in 156,566 control chromosomes in the GnomAD database, including 15 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.012 (15 hom., cov: 33)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: AGT NM_001384479.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.316

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0118 (1792/152300) while in subpopulation NFE AF= 0.0208 (1415/68012). AF 95% confidence interval is 0.0199. There are 15 homozygotes in gnomad4. There are 764 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001384479.1	c.*575del		3_prime_UTR_variant	5/5	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.*575del		3_prime_UTR_variant	5/5		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.*575del		3_prime_UTR_variant	5/5	1	NM_001384479.1	ENSP00000355627	P1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1793 AN: 152180 Hom.: 15 Cov.: 33

Gnomad AFR AF: 0.00333

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00706

Gnomad ASJ AF: 0.00749

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00600

Gnomad FIN AF: 0.00574

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0208

Gnomad OTH AF: 0.00525

GnomAD4 exome AF: 0.0110 AC: 47 AN: 4266 Hom.: 0 Cov.: 0 AF XY: 0.0105 AC XY: 23 AN XY: 2186

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00540

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00541

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0143

Gnomad4 OTH exome AF: 0.0286

GnomAD4 genome AF: 0.0118 AC: 1792 AN: 152300 Hom.: 15 Cov.: 33 AF XY: 0.0103 AC XY: 764 AN XY: 74482

Gnomad4 AFR AF: 0.00332

Gnomad4 AMR AF: 0.00699

Gnomad4 ASJ AF: 0.00749

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.00574

Gnomad4 NFE AF: 0.0208

Gnomad4 OTH AF: 0.00520

Alfa AF: 0.0173 Hom.: 2

Bravo AF: 0.0120

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs55720804; hg19: chr1-230838311;