rs5049

Positions:

• chr1-230714337-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000412344.1(ENSG00000244137):​n.381-3484G>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 0.161 in 152,278 control chromosomes in the GnomAD database, including 2,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2312 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.49

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-230714337-C-T is Benign according to our data. Variant chr1-230714337-C-T is described in ClinVar as [Benign]. Clinvar id is 296097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001382817.3	c.-30-3484G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000412344.1	n.381-3484G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24448 AN: 152014 Hom.: 2302 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0878

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: 0.141

GnomAD4 exome AF: 0.158 AC: 23 AN: 146 Hom.: 2 Cov.: 0 AF XY: 0.196 AC XY: 20 AN XY: 102

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.161 AC: 24487 AN: 152132 Hom.: 2312 Cov.: 32 AF XY: 0.162 AC XY: 12045 AN XY: 74372

Gnomad4 AFR AF: 0.266

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.138

Alfa AF: 0.149 Hom.: 252

Bravo AF: 0.163

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 18, 2019	This variant is associated with the following publications: (PMID: 14597849, 12145290) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Renal tubular dysgenesis Benign:1

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	-0.69
CADD	Benign	0.79
DANN	Benign	0.92

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs5049; hg19: chr1-230850083;