rs2493137

Positions:

• chr1-230716370-T-C

Variant summary

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

The ENST00000412344.1(ENSG00000244137):​n.381-5517A>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 0.418 in 152,026 control chromosomes in the GnomAD database, including 14,458 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 0.42 (14458 hom., cov: 33)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-5517A>G		intron_variant			NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000412344.1	n.381-5517A>G		intron_variant, non_coding_transcript_variant		3
AGT	ENST00000681269.1	c.-30-5517A>G		intron_variant				ENSP00000505985	P1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63547 AN: 151908 Hom.: 14435 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.418 AC: 63621 AN: 152026 Hom.: 14458 Cov.: 33 AF XY: 0.422 AC XY: 31332 AN XY: 74312

Gnomad4 AFR AF: 0.567

Gnomad4 AMR AF: 0.504

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.654

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.337

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.418

Alfa AF: 0.340 Hom.: 12519

Bravo AF: 0.443

Asia WGS AF: 0.529 AC: 1838 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.8
DANN	Benign	0.83

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2493137; hg19: chr1-230852116;