rs61762526

chr1-230703108-C-Achr1-230703108-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001384479.1(AGT):c.*33G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,607,926 control chromosomes in the GnomAD database, including 3 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 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00039 (3 hom.)
• Consequence: AGT NM_001384479.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.738

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 Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1	c.*33G>T		3_prime_UTR_variant	5/5	ENST00000366667.6
AGT	NM_001382817.3	c.*33G>T		3_prime_UTR_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6	c.*33G>T		3_prime_UTR_variant	5/5	1	NM_001384479.1	P1

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152212 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000723

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000414 AC: 102 AN: 246302 Hom.: 0 AF XY: 0.000487 AC XY: 65 AN XY: 133342

Gnomad AFR exome AF: 0.000252

Gnomad AMR exome AF: 0.0000876

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000112

Gnomad SAS exome AF: 0.000889

Gnomad FIN exome AF: 0.000144

Gnomad NFE exome AF: 0.000568

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000392 AC: 570 AN: 1455596 Hom.: 3 Cov.: 30 AF XY: 0.000453 AC XY: 328 AN XY: 723650

Gnomad4 AFR exome AF: 0.0000600

Gnomad4 AMR exome AF: 0.0000676

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000710

Gnomad4 FIN exome AF: 0.000114

Gnomad4 NFE exome AF: 0.000434

Gnomad4 OTH exome AF: 0.000200

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152330 Hom.: 0 Cov.: 33 AF XY: 0.000255 AC XY: 19 AN XY: 74494

Gnomad4 AFR AF: 0.0000721

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000299 Hom.: 0

Bravo AF: 0.000204

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	5.1
Dann	Benign	0.88
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs61762526; hg19: chr1-230838854; COSMIC: COSV100794257;