rs2478516

chr1-230732906-T-C

Variant summary

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

The ENST00000412344.1(ENSG00000244137):n.381-22053A>G 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 0.176 in 152,024 control chromosomes in the GnomAD database, including 2,454 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 0.18 (2454 hom., cov: 31)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001382817.3	c.-31+12609A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000412344.1	n.381-22053A>G		intron_variant, non_coding_transcript_variant		3
AGT	ENST00000681269.1	c.-31+12609A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26742 AN: 151906 Hom.: 2453 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.258

Gnomad FIN AF: 0.124

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.149

Gnomad OTH AF: 0.180

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

GnomAD4 genome AF: 0.176 AC: 26766 AN: 152024 Hom.: 2454 Cov.: 31 AF XY: 0.180 AC XY: 13346 AN XY: 74290

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.188

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.224

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.124

Gnomad4 NFE AF: 0.149

Gnomad4 OTH AF: 0.177

Alfa AF: 0.142 Hom.: 1189

Bravo AF: 0.178

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.12
Dann	Benign	0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2478516; hg19: chr1-230868652;