rs1326886

Positions:

• chr1-230724014-A-G

Variant summary

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

The ENST00000412344.1(ENSG00000244137):​n.381-13161T>C 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 0.156 in 152,226 control chromosomes in the GnomAD database, including 2,438 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 0.16 (2438 hom., cov: 33)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.580

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-13161T>C		intron_variant			NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000412344.1	n.381-13161T>C		intron_variant, non_coding_transcript_variant		3
AGT	ENST00000681269.1	c.-30-13161T>C		intron_variant				ENSP00000505985	P1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23615 AN: 152108 Hom.: 2424 Cov.: 33

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.257

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.0922

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.156 AC: 23675 AN: 152226 Hom.: 2438 Cov.: 33 AF XY: 0.159 AC XY: 11836 AN XY: 74440

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.258

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.486

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.0922

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.160

Alfa AF: 0.129 Hom.: 191

Bravo AF: 0.175

Asia WGS AF: 0.350 AC: 1218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
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: rs1326886; hg19: chr1-230859760;