1-230712043-G-A

Position:

• chr1-230712043-G-A

Variant summary

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

The NM_001384479.1(AGT):​c.-30-1190C>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

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=-0.87).
• 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/exons	MANE	UniProt
AGT	NM_001384479.1	c.-30-1190C>T		intron_variant		ENST00000366667.6
AGT	NM_001382817.3	c.-30-1190C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6	c.-30-1190C>T		intron_variant		1	NM_001384479.1	P1
	ENST00000412344.1	n.381-1190C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0472

Gnomad4 AMR AF: 0.146

Gnomad4 ASJ AF: 0.0358

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0423

Gnomad4 NFE AF: 0.0842

Gnomad4 OTH AF: 0.0791

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

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: rs11122578; hg19: chr1-230847789;