1-230713444-C-T

Position:

• chr1-230713444-C-T

Variant summary

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

The ENST00000366667.6(AGT):​c.-31+642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 152,072 control chromosomes in the GnomAD database, including 15,132 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 0.44 (15132 hom., cov: 33)
• Consequence: AGT ENST00000366667.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-31+642G>A		intron_variant		ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-2591G>A		intron_variant			NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.-31+642G>A		intron_variant		1	NM_001384479.1	ENSP00000355627	P1
	ENST00000412344.1	n.381-2591G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66309 AN: 151954 Hom.: 15119 Cov.: 33

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.412

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

GnomAD4 genome AF: 0.436 AC: 66355 AN: 152072 Hom.: 15132 Cov.: 33 AF XY: 0.440 AC XY: 32674 AN XY: 74322

Gnomad4 AFR AF: 0.524

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.409

Alfa AF: 0.415 Hom.: 1995

Bravo AF: 0.447

Asia WGS AF: 0.557 AC: 1935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.43
DANN	Benign	0.57

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: rs7539020; hg19: chr1-230849190;