rs11122577

chr1-230711810-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384479.1(AGT):c.-30-957G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 127,308 control chromosomes in the GnomAD database, including 2,053 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 0.19 (2053 hom., cov: 29)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1	c.-30-957G>T		intron_variant		ENST00000366667.6
AGT	NM_001382817.3	c.-30-957G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6	c.-30-957G>T		intron_variant		1	NM_001384479.1	P1
	ENST00000412344.1	n.381-957G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.190 AC: 24119 AN: 127254 Hom.: 2053 Cov.: 29

Gnomad AFR AF: 0.172

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.221

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.148

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.189 AC: 24115 AN: 127308 Hom.: 2053 Cov.: 29 AF XY: 0.193 AC XY: 11888 AN XY: 61448

Gnomad4 AFR AF: 0.172

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.186

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.179

Gnomad4 OTH AF: 0.190

Alfa AF: 0.173 Hom.: 422

Bravo AF: 0.156

Asia WGS AF: 0.141 AC: 486 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11122577; hg19: chr1-230847556;