rs11122575

Variant names:

• chr1-230704523-A-G
• rs11122575
• NM_001384479.1:c.1098-186T>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.1098-186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 152,268 control chromosomes in the GnomAD database, including 796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.080 (796 hom., cov: 33)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.30
• Publications: 7 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=-0.91).
• BP6: Variant 1-230704523-A-G is Benign according to our data. Variant chr1-230704523-A-G is described in ClinVar as Benign. ClinVar VariationId is 1226630.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.334 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.1098-186T>C		intron_variant	Intron 3 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.1098-186T>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.1098-186T>C		intron_variant	Intron 3 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12241 AN: 152150 Hom.: 796 Cov.: 33

Gnomad AFR AF: 0.0409

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.106

Gnomad FIN AF: 0.0424

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0798

Gnomad OTH AF: 0.0726

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

GnomAD4 genome AF: 0.0804 AC: 12247 AN: 152268 Hom.: 796 Cov.: 33 AF XY: 0.0817 AC XY: 6079 AN XY: 74448

African (AFR) AF: 0.0409 AC: 1701 AN: 41564

American (AMR) AF: 0.136 AC: 2082 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1794 AN: 5168

South Asian (SAS) AF: 0.105 AC: 509 AN: 4828

European-Finnish (FIN) AF: 0.0424 AC: 450 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0798 AC: 5426 AN: 68010

Other (OTH) AF: 0.0751 AC: 159 AN: 2116

Alfa AF: 0.0765 Hom.: 67

Bravo AF: 0.0880

Asia WGS AF: 0.223 AC: 773 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

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	-0.91
CADD	Benign	0.021
DANN	Benign	0.32
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs11122575; hg19: chr1-230840269;