rs4628514

chr1-230720372-T-C

Variant summary

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

The ENST00000412344.1(ENSG00000244137):n.381-9519A>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 0.199 in 152,124 control chromosomes in the GnomAD database, including 4,158 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 0.20 (4158 hom., cov: 33)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001382817.3	c.-30-9519A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000412344.1	n.381-9519A>G		intron_variant, non_coding_transcript_variant		3
AGT	ENST00000681269.1	c.-30-9519A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30231 AN: 152006 Hom.: 4133 Cov.: 33

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0921

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.199 AC: 30322 AN: 152124 Hom.: 4158 Cov.: 33 AF XY: 0.201 AC XY: 14979 AN XY: 74358

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.490

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.0921

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.193

Alfa AF: 0.194 Hom.: 625

Bravo AF: 0.224

Asia WGS AF: 0.365 AC: 1268 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.66
Dann	Benign	0.59

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4628514; hg19: chr1-230856118;