rs3789678

Positions:

• chr1-230713736-C-T

Variant summary

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

The NM_001384479.1(AGT):​c.-31+350G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 152,126 control chromosomes in the GnomAD database, including 2,064 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 0.15 (2064 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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]

ENSG00000244137 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-31+350G>A		intron_variant		ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-2883G>A		intron_variant			NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.-31+350G>A		intron_variant		1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23415 AN: 152008 Hom.: 2056 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.154 AC: 23448 AN: 152126 Hom.: 2064 Cov.: 32 AF XY: 0.155 AC XY: 11533 AN XY: 74352

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.0885

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.132

Alfa AF: 0.143 Hom.: 214

Bravo AF: 0.155

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs3789678; hg19: chr1-230849482;