chr1-230725832-C-T

Variant names:

• chr1-230725832-C-T
• rs7515609
• NM_001382817.3:c.-30-14979G>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.-30-14979G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,050 control chromosomes in the GnomAD database, including 2,631 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 0.16 (2631 hom., cov: 32)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-14979G>A		intron_variant	Intron 1 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000681269.1	c.-30-14979G>A		intron_variant	Intron 1 of 4			ENSP00000505985.1
ENSG00000244137	ENST00000412344.1	n.381-14979G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24589 AN: 151930 Hom.: 2617 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.0597

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.155

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

GnomAD4 genome AF: 0.162 AC: 24659 AN: 152050 Hom.: 2631 Cov.: 32 AF XY: 0.165 AC XY: 12296 AN XY: 74310

African (AFR) AF: 0.204 AC: 8453 AN: 41432

American (AMR) AF: 0.262 AC: 3999 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 207 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2520 AN: 5152

South Asian (SAS) AF: 0.211 AC: 1014 AN: 4814

European-Finnish (FIN) AF: 0.0922 AC: 976 AN: 10586

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.104 AC: 7054 AN: 68002

Other (OTH) AF: 0.164 AC: 347 AN: 2110

Alfa AF: 0.113 Hom.: 1514

Bravo AF: 0.181

Asia WGS AF: 0.357 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.090
DANN	Benign	0.30
PhyloP100		-1.7

Splicing

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

Other links and lift over

dbSNP: rs7515609; hg19: chr1-230861578;