rs2478518

Variant names:

• chr1-230732124-G-C
• rs2478518
• NM_001382817.3:c.-31+13391C>G

Your query was ambiguous. Multiple possible variants found:

• chr1-230732124-G-C
• chr1-230732124-G-T

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+13391C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,794 control chromosomes in the GnomAD database, including 3,906 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 0.21 (3906 hom., cov: 32)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 9 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=-1.06).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 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.-31+13391C>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.-31+13391C>G		intron	N/A	ENSP00000505985.1	P01019
	CAPN9-AS1	ENST00000412344.1	TSL:3	n.381-21271C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31593 AN: 151676 Hom.: 3890 Cov.: 32

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.230

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.137

Gnomad OTH AF: 0.211

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

GnomAD4 genome AF: 0.209 AC: 31665 AN: 151794 Hom.: 3906 Cov.: 32 AF XY: 0.212 AC XY: 15732 AN XY: 74152

African (AFR) AF: 0.279 AC: 11566 AN: 41386

American (AMR) AF: 0.308 AC: 4690 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3466

East Asian (EAS) AF: 0.488 AC: 2503 AN: 5130

South Asian (SAS) AF: 0.231 AC: 1108 AN: 4802

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10538

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.137 AC: 9310 AN: 67938

Other (OTH) AF: 0.219 AC: 460 AN: 2096

Alfa AF: 0.178 Hom.: 350

Bravo AF: 0.231

Asia WGS AF: 0.388 AC: 1349 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.60
DANN	Benign	0.32
PhyloP100		-2.2

Splicing

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

Other links and lift over

dbSNP: rs2478518; hg19: chr1-230867870;