chr1-230729480-G-T

Variant names:

• chr1-230729480-G-T
• rs4847008
• NM_001382817.3:c.-31+16035C>A

Variant summary

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

The NM_001382817.3(AGT):​c.-31+16035C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 152,042 control chromosomes in the GnomAD database, including 7,601 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 0.29 (7601 hom., cov: 32)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 8 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)

ENSG00000244137 (HGNC:58238):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001382817.3		c.-31+16035C>A		intron	N/A	NP_001369746.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000681269.1		c.-31+16035C>A		intron	N/A	ENSP00000505985.1
	ENSG00000244137	ENST00000412344.1	TSL:3	n.381-18627C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44653 AN: 151924 Hom.: 7563 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.184

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.283

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

GnomAD4 genome AF: 0.294 AC: 44748 AN: 152042 Hom.: 7601 Cov.: 32 AF XY: 0.299 AC XY: 22249 AN XY: 74338

African (AFR) AF: 0.376 AC: 15580 AN: 41468

American (AMR) AF: 0.380 AC: 5799 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3468

East Asian (EAS) AF: 0.665 AC: 3428 AN: 5158

South Asian (SAS) AF: 0.415 AC: 1997 AN: 4816

European-Finnish (FIN) AF: 0.184 AC: 1952 AN: 10590

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14681 AN: 67962

Other (OTH) AF: 0.290 AC: 613 AN: 2114

Alfa AF: 0.277 Hom.: 1082

Bravo AF: 0.313

Asia WGS AF: 0.546 AC: 1899 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.72
DANN	Benign	0.33
PhyloP100		-0.23

Splicing

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

Other links and lift over

dbSNP: rs4847008; hg19: chr1-230865226;