1-230705763-A-G

Variant names:

• chr1-230705763-A-G
• rs2478523
• NM_001384479.1:c.1097+170T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001384479.1(AGT):​c.1097+170T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 152,124 control chromosomes in the GnomAD database, including 22,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.50 (22113 hom., cov: 33)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.15
• Publications: 19 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-230705763-A-G is Benign according to our data. Variant chr1-230705763-A-G is described in ClinVar as Benign. ClinVar VariationId is 1288046.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.1097+170T>C		intron_variant	Intron 3 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.1097+170T>C		intron_variant	Intron 3 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.1097+170T>C		intron_variant	Intron 3 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.500 AC: 76024 AN: 152006 Hom.: 22057 Cov.: 33

Gnomad AFR AF: 0.804

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.518

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.515

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.334

Gnomad OTH AF: 0.487

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

GnomAD4 genome AF: 0.501 AC: 76140 AN: 152124 Hom.: 22113 Cov.: 33 AF XY: 0.505 AC XY: 37533 AN XY: 74356

African (AFR) AF: 0.805 AC: 33402 AN: 41518

American (AMR) AF: 0.518 AC: 7923 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3472

East Asian (EAS) AF: 0.495 AC: 2550 AN: 5148

South Asian (SAS) AF: 0.514 AC: 2477 AN: 4820

European-Finnish (FIN) AF: 0.398 AC: 4222 AN: 10596

Middle Eastern (MID) AF: 0.483 AC: 141 AN: 292

European-Non Finnish (NFE) AF: 0.334 AC: 22712 AN: 67972

Other (OTH) AF: 0.489 AC: 1032 AN: 2112

Alfa AF: 0.386 Hom.: 20872

Bravo AF: 0.521

Asia WGS AF: 0.517 AC: 1797 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.48
PhyloP100		-3.1
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: rs2478523; hg19: chr1-230841509;