NM_001382817.3:c.-30-9519A>G

Variant names:

• chr1-230720372-T-C
• rs4628514
• NM_001382817.3:c.-30-9519A>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.-30-9519A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 152,124 control chromosomes in the GnomAD database, including 4,158 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 0.20 (4158 hom., cov: 33)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23
• Publications: 7 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)

CAPN9-AS1 (HGNC:58238):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001382817.3		c.-30-9519A>G		intron	N/A	NP_001369746.2	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000681269.1		c.-30-9519A>G		intron	N/A	ENSP00000505985.1	P01019
	CAPN9-AS1	ENST00000412344.1	TSL:3	n.381-9519A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30231 AN: 152006 Hom.: 4133 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.199 AC: 30322 AN: 152124 Hom.: 4158 Cov.: 33 AF XY: 0.201 AC XY: 14979 AN XY: 74358

African (AFR) AF: 0.330 AC: 13700 AN: 41478

American (AMR) AF: 0.280 AC: 4281 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0617 AC: 214 AN: 3470

East Asian (EAS) AF: 0.490 AC: 2523 AN: 5152

South Asian (SAS) AF: 0.211 AC: 1020 AN: 4824

European-Finnish (FIN) AF: 0.0921 AC: 975 AN: 10586

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7108 AN: 68006

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.194 Hom.: 625

Bravo AF: 0.224

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.66
DANN	Benign	0.59
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs4628514; hg19: chr1-230856118;