rs2478516

Variant names:

• chr1-230732906-T-C
• rs2478516
• NM_001382817.3:c.-31+12609A>G

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+12609A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 152,024 control chromosomes in the GnomAD database, including 2,454 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 0.18 (2454 hom., cov: 31)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-31+12609A>G		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.-31+12609A>G		intron_variant	Intron 1 of 4			ENSP00000505985.1
ENSG00000244137	ENST00000412344.1	n.381-22053A>G		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26742 AN: 151906 Hom.: 2453 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.176 AC: 26766 AN: 152024 Hom.: 2454 Cov.: 31 AF XY: 0.180 AC XY: 13346 AN XY: 74290

African (AFR) AF: 0.213 AC: 8838 AN: 41448

American (AMR) AF: 0.188 AC: 2873 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3468

East Asian (EAS) AF: 0.224 AC: 1155 AN: 5160

South Asian (SAS) AF: 0.258 AC: 1240 AN: 4814

European-Finnish (FIN) AF: 0.124 AC: 1312 AN: 10560

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.149 AC: 10134 AN: 67984

Other (OTH) AF: 0.177 AC: 373 AN: 2110

Alfa AF: 0.143 Hom.: 1294

Bravo AF: 0.178

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.12
DANN	Benign	0.28
PhyloP100		-2.5

Splicing

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

Other links and lift over

dbSNP: rs2478516; hg19: chr1-230868652;