1-230714272-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000412344.1(ENSG00000244137):n.381-3419G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0385 in 152,474 control chromosomes in the GnomAD database, including 161 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (161 hom., cov: 32)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.65

Genes affected

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 1-230714272-C-T is Benign according to our data. Variant chr1-230714272-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 296094.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-230714272-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001382817.3	c.-30-3419G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000412344.1	n.381-3419G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0385 AC: 5862 AN: 152168 Hom.: 161 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0545

Gnomad SAS AF: 0.0416

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0521

GnomAD4 exome AF: 0.0426 AC: 8 AN: 188 Hom.: 0 Cov.: 0 AF XY: 0.0352 AC XY: 5 AN XY: 142

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.125

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0432

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0385 AC: 5867 AN: 152286 Hom.: 161 Cov.: 32 AF XY: 0.0388 AC XY: 2888 AN XY: 74456

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.0668

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.0544

Gnomad4 SAS AF: 0.0421

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.0515

Alfa AF: 0.0421 Hom.: 219

Bravo AF: 0.0422

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Renal tubular dysgenesis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	0.018
Dann	Benign	0.55
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11568020; hg19: chr1-230850018;