chr1-230714053-A-G

Position:

• chr1-230714053-A-G

Variant summary

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

The NM_001384479.1(AGT):​c.-31+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,938 control chromosomes in the GnomAD database, including 28,063 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 0.58 (28057 hom., cov: 31)
  • Exomes 𝑓: 0.57 (6 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580

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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001384479.1	c.-31+33T>C		intron_variant		ENST00000366667.6
AGT	NM_001382817.3	c.-30-3200T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGT	ENST00000366667.6	c.-31+33T>C		intron_variant		1	NM_001384479.1	P1
	ENST00000412344.1	n.381-3200T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87899 AN: 151778 Hom.: 28002 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.575 AC: 23 AN: 40 Hom.: 6 Cov.: 0 AF XY: 0.625 AC XY: 20 AN XY: 32

Gnomad4 NFE exome AF: 0.575

GnomAD4 genome AF: 0.579 AC: 88011 AN: 151898 Hom.: 28057 Cov.: 31 AF XY: 0.584 AC XY: 43337 AN XY: 74210

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.640

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.622

Gnomad4 FIN AF: 0.444

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.566

Alfa AF: 0.462 Hom.: 16852

Bravo AF: 0.606

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.42
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs2148582; hg19: chr1-230849799;