rs11122578

Variant names:

• chr1-230712043-G-A
• rs11122578
• NM_001384479.1:c.-30-1190C>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.-30-1190C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 152,160 control chromosomes in the GnomAD database, including 848 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 0.086 (848 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00100
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-30-1190C>T		intron_variant	Intron 1 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-1190C>T		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.-30-1190C>T		intron_variant	Intron 1 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.0859 AC: 13063 AN: 152042 Hom.: 850 Cov.: 32

Gnomad AFR AF: 0.0472

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.0785

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

GnomAD4 genome AF: 0.0859 AC: 13065 AN: 152160 Hom.: 848 Cov.: 32 AF XY: 0.0875 AC XY: 6508 AN XY: 74376

African (AFR) AF: 0.0472 AC: 1963 AN: 41548

American (AMR) AF: 0.146 AC: 2229 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 124 AN: 3464

East Asian (EAS) AF: 0.351 AC: 1802 AN: 5130

South Asian (SAS) AF: 0.110 AC: 533 AN: 4826

European-Finnish (FIN) AF: 0.0423 AC: 449 AN: 10612

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0842 AC: 5722 AN: 67984

Other (OTH) AF: 0.0791 AC: 167 AN: 2110

Alfa AF: 0.0879 Hom.: 137

Bravo AF: 0.0943

Asia WGS AF: 0.219 AC: 759 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.9
DANN	Benign	0.60
PhyloP100		-0.0010
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: rs11122578; hg19: chr1-230847789;