chr1-230714895-A-G

Variant names:

• chr1-230714895-A-G
• rs2071406
• NM_001382817.3:c.-30-4042T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382817.3(AGT):​c.-30-4042T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,230 control chromosomes in the GnomAD database, including 2,039 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 0.13 (2039 hom., cov: 32)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.594
• Publications: 8 publications found

Genes affected

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]

AGT Gene-Disease associations (from GenCC):

• renal tubular dysgenesis of genetic origin

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000244137 (HGNC:58238):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-4042T>C		intron_variant	Intron 1 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000681269.1	c.-30-4042T>C		intron_variant	Intron 1 of 4			ENSP00000505985.1
ENSG00000244137	ENST00000412344.1	n.381-4042T>C		intron_variant	Intron 1 of 1	3
AGT	ENST00000679738.1	n.-840T>C		upstream_gene_variant				ENSP00000505063.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20028 AN: 152112 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.158

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0792

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0487

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.132 AC: 20079 AN: 152230 Hom.: 2039 Cov.: 32 AF XY: 0.133 AC XY: 9934 AN XY: 74434

African (AFR) AF: 0.275 AC: 11418 AN: 41496

American (AMR) AF: 0.159 AC: 2432 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 443 AN: 3472

East Asian (EAS) AF: 0.140 AC: 724 AN: 5188

South Asian (SAS) AF: 0.111 AC: 536 AN: 4824

European-Finnish (FIN) AF: 0.0792 AC: 841 AN: 10612

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0487 AC: 3309 AN: 68014

Other (OTH) AF: 0.142 AC: 300 AN: 2116

Alfa AF: 0.0848 Hom.: 1234

Bravo AF: 0.148

Asia WGS AF: 0.159 AC: 552 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	4.5
DANN	Benign	0.60
PhyloP100		0.59
PromoterAI		0.014	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2071406; hg19: chr1-230850641;