1-230715298-T-C

Position:

• chr1-230715298-T-C

Variant summary

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

The ENST00000412344.1(ENSG00000244137):​n.381-4445A>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 0.145 in 152,132 control chromosomes in the GnomAD database, including 1,757 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 0.15 (1757 hom., cov: 32)
• Consequence: ENST00000412344.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995

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 (AFR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AGT	NM_001382817.3	c.-30-4445A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000412344.1	n.381-4445A>G		intron_variant, non_coding_transcript_variant		3
AGT	ENST00000681269.1	c.-30-4445A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22098 AN: 152014 Hom.: 1751 Cov.: 32

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0859

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.145 AC: 22128 AN: 152132 Hom.: 1757 Cov.: 32 AF XY: 0.147 AC XY: 10911 AN XY: 74372

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.0859

Gnomad4 EAS AF: 0.174

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.113

Gnomad4 OTH AF: 0.129

Alfa AF: 0.138 Hom.: 195

Bravo AF: 0.146

Asia WGS AF: 0.193 AC: 672 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	1.1
DANN	Benign	0.34

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11122580; hg19: chr1-230851044;