1-230713422-C-T

Variant names:

• chr1-230713422-C-T
• rs7539013
• NM_001384479.1:c.-31+664G>A

Variant summary

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

The NM_001384479.1(AGT):​c.-31+664G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,064 control chromosomes in the GnomAD database, including 15,132 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 0.44 (15132 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77
• 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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384479.1. 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_001384479.1	MANE Select	c.-31+664G>A		intron	N/A	NP_001371408.1	P01019
	AGT	NM_001382817.3		c.-30-2569G>A		intron	N/A	NP_001369746.2	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.-31+664G>A		intron	N/A	ENSP00000355627.5	P01019
	AGT	ENST00000680041.1		c.-156+664G>A		intron	N/A	ENSP00000504866.1	P01019
	AGT	ENST00000681269.1		c.-30-2569G>A		intron	N/A	ENSP00000505985.1	P01019

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66307 AN: 151946 Hom.: 15119 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.436 AC: 66353 AN: 152064 Hom.: 15132 Cov.: 32 AF XY: 0.440 AC XY: 32675 AN XY: 74312

African (AFR) AF: 0.524 AC: 21705 AN: 41456

American (AMR) AF: 0.473 AC: 7229 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1052 AN: 3466

East Asian (EAS) AF: 0.697 AC: 3598 AN: 5160

South Asian (SAS) AF: 0.493 AC: 2374 AN: 4814

European-Finnish (FIN) AF: 0.365 AC: 3866 AN: 10584

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25201 AN: 67986

Other (OTH) AF: 0.411 AC: 868 AN: 2114

Alfa AF: 0.431 Hom.: 2044

Bravo AF: 0.447

Asia WGS AF: 0.558 AC: 1939 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.3
DANN	Benign	0.74
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7539013; hg19: chr1-230849168;