1-230708375-G-A

Variant names:

• chr1-230708375-G-A
• rs2478545
• NM_001384479.1:c.829+1620C>T

Variant summary

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

The NM_001384479.1(AGT):​c.829+1620C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,982 control chromosomes in the GnomAD database, including 8,051 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 0.31 (8051 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.196
• Publications: 24 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.455 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001384479.1	MANE Select	c.829+1620C>T		intron	N/A	NP_001371408.1
	AGT	NM_001382817.3		c.829+1620C>T		intron	N/A	NP_001369746.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.829+1620C>T		intron	N/A	ENSP00000355627.5
	AGT	ENST00000679854.1		n.2960C>T		non_coding_transcript_exon	Exon 2 of 6
	AGT	ENST00000680041.1		c.829+1620C>T		intron	N/A	ENSP00000504866.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47234 AN: 151864 Hom.: 8035 Cov.: 32

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.218

Gnomad OTH AF: 0.320

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

GnomAD4 genome AF: 0.311 AC: 47293 AN: 151982 Hom.: 8051 Cov.: 32 AF XY: 0.314 AC XY: 23351 AN XY: 74288

African (AFR) AF: 0.460 AC: 19056 AN: 41396

American (AMR) AF: 0.344 AC: 5262 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1086 AN: 3470

East Asian (EAS) AF: 0.312 AC: 1605 AN: 5150

South Asian (SAS) AF: 0.281 AC: 1353 AN: 4818

European-Finnish (FIN) AF: 0.289 AC: 3050 AN: 10568

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.218 AC: 14830 AN: 67988

Other (OTH) AF: 0.326 AC: 688 AN: 2108

Alfa AF: 0.250 Hom.: 16579

Bravo AF: 0.326

Asia WGS AF: 0.303 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.99
DANN	Benign	0.34
PhyloP100		-0.20
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
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: rs2478545; hg19: chr1-230844121;