rs55720804

Variant names:

• chr1-230702565-AG-A
• rs55720804
• NM_001384479.1:c.*575delC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001384479.1(AGT):​c.*575delC 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
• Publications: 1 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 -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384479.1. 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
	AGT	NM_001384479.1	MANE Select	c.*575delC		3_prime_UTR	Exon 5 of 5	NP_001371408.1	P01019
	AGT	NM_001382817.3		c.*575delC		3_prime_UTR	Exon 5 of 5	NP_001369746.2	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.*575delC		3_prime_UTR	Exon 5 of 5	ENSP00000355627.5	P01019
	AGT	ENST00000680041.1		c.*575delC		3_prime_UTR	Exon 5 of 5	ENSP00000504866.1	P01019
	AGT	ENST00000681269.1		c.*575delC		3_prime_UTR	Exon 5 of 5	ENSP00000505985.1	P01019

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

African (AFR) AF: 0.00 AC: 0 AN: 16

American (AMR) AF: 0.00540 AC: 6 AN: 1112

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12

East Asian (EAS) AF: 0.00 AC: 0 AN: 154

South Asian (SAS) AF: 0.00541 AC: 2 AN: 370

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0143 AC: 35 AN: 2442

Other (OTH) AF: 0.0286 AC: 4 AN: 140

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

African (AFR) AF: 0.00332 AC: 138 AN: 41578

American (AMR) AF: 0.00699 AC: 107 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00749 AC: 26 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4826

European-Finnish (FIN) AF: 0.00574 AC: 61 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0208 AC: 1415 AN: 68012

Other (OTH) AF: 0.00520 AC: 11 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs55720804; hg19: chr1-230838311; COSMIC: COSV64184723;