1-230712956-C-T

Variant names:

• chr1-230712956-C-T
• rs2004776
• NM_001384479.1:c.-31+1130G>A

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.-31+1130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,948 control chromosomes in the GnomAD database, including 9,007 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (9007 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.38
• Publications: 35 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)

ENSG00000244137 (HGNC:58238):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 1-230712956-C-T is Benign according to our data. Variant chr1-230712956-C-T is described in ClinVar as Benign. ClinVar VariationId is 1258430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-31+1130G>A		intron_variant	Intron 1 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-2103G>A		intron_variant	Intron 1 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.-31+1130G>A		intron_variant	Intron 1 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48939 AN: 151830 Hom.: 8988 Cov.: 32

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.582

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.174

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.244

Gnomad OTH AF: 0.305

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

GnomAD4 genome AF: 0.322 AC: 48993 AN: 151948 Hom.: 9007 Cov.: 32 AF XY: 0.323 AC XY: 23994 AN XY: 74282

African (AFR) AF: 0.458 AC: 18979 AN: 41404

American (AMR) AF: 0.359 AC: 5489 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 555 AN: 3470

East Asian (EAS) AF: 0.582 AC: 2982 AN: 5122

South Asian (SAS) AF: 0.357 AC: 1720 AN: 4816

European-Finnish (FIN) AF: 0.174 AC: 1839 AN: 10592

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16583 AN: 67956

Other (OTH) AF: 0.303 AC: 638 AN: 2108

Alfa AF: 0.257 Hom.: 6893

Bravo AF: 0.342

Asia WGS AF: 0.456 AC: 1584 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 17, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 31201268) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.66
DANN	Benign	0.49
PhyloP100		-1.4
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: rs2004776; hg19: chr1-230848702;