rs1326886

Variant names:

• chr1-230724014-A-G
• rs1326886
• NM_001382817.3:c.-30-13161T>C

Variant summary

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

The NM_001382817.3(AGT):​c.-30-13161T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,226 control chromosomes in the GnomAD database, including 2,438 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 (2438 hom., cov: 33)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580
• 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)

CAPN9-AS1 (HGNC:58238):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 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.-30-13161T>C		intron	N/A	NP_001369746.2	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000681269.1		c.-30-13161T>C		intron	N/A	ENSP00000505985.1	P01019
	CAPN9-AS1	ENST00000412344.1	TSL:3	n.381-13161T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23615 AN: 152108 Hom.: 2424 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.156 AC: 23675 AN: 152226 Hom.: 2438 Cov.: 33 AF XY: 0.159 AC XY: 11836 AN XY: 74440

African (AFR) AF: 0.185 AC: 7679 AN: 41532

American (AMR) AF: 0.258 AC: 3944 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3466

East Asian (EAS) AF: 0.486 AC: 2510 AN: 5164

South Asian (SAS) AF: 0.197 AC: 953 AN: 4826

European-Finnish (FIN) AF: 0.0922 AC: 979 AN: 10620

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.103 AC: 6978 AN: 68014

Other (OTH) AF: 0.160 AC: 338 AN: 2114

Alfa AF: 0.129 Hom.: 191

Bravo AF: 0.175

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.59
PhyloP100		0.58

Splicing

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

Other links and lift over

dbSNP: rs1326886; hg19: chr1-230859760;