rs11568054

Variant names:

• chr1-230709809-G-A
• rs11568054
• NM_001384479.1:c.829+186C>T

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.829+186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.035 in 152,340 control chromosomes in the GnomAD database, including 142 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.035 (142 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.13
• 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)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-230709809-G-A is Benign according to our data. Variant chr1-230709809-G-A is described in ClinVar as Benign. ClinVar VariationId is 1231565.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.829+186C>T		intron_variant	Intron 2 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.829+186C>T		intron_variant	Intron 2 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.829+186C>T		intron_variant	Intron 2 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5328 AN: 152222 Hom.: 142 Cov.: 32

Gnomad AFR AF: 0.00914

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.0434

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0576

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0350 AC: 5328 AN: 152340 Hom.: 142 Cov.: 32 AF XY: 0.0335 AC XY: 2496 AN XY: 74486

African (AFR) AF: 0.00911 AC: 379 AN: 41582

American (AMR) AF: 0.0254 AC: 388 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0167 AC: 58 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4828

European-Finnish (FIN) AF: 0.0434 AC: 461 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0576 AC: 3922 AN: 68032

Other (OTH) AF: 0.0326 AC: 69 AN: 2114

Alfa AF: 0.0451 Hom.: 74

Bravo AF: 0.0319

Asia WGS AF: 0.00635 AC: 22 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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.2
DANN	Benign	0.69
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism

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: rs11568054; hg19: chr1-230845555;