chr1-230715298-T-C

Variant names:

• chr1-230715298-T-C
• rs11122580
• NM_001382817.3:c.-30-4445A>G

Variant summary

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

The NM_001382817.3(AGT):​c.-30-4445A>G variant causes a intron 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: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.995
• Publications: 6 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=-0.96).
• 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 rank	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-4445A>G		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.-30-4445A>G		intron_variant	Intron 1 of 4			ENSP00000505985.1
ENSG00000244137	ENST00000412344.1	n.381-4445A>G		intron_variant	Intron 1 of 1	3

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

African (AFR) AF: 0.213 AC: 8832 AN: 41470

American (AMR) AF: 0.122 AC: 1873 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0859 AC: 298 AN: 3470

East Asian (EAS) AF: 0.174 AC: 898 AN: 5168

South Asian (SAS) AF: 0.208 AC: 1003 AN: 4822

European-Finnish (FIN) AF: 0.107 AC: 1130 AN: 10600

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7717 AN: 68000

Other (OTH) AF: 0.129 AC: 272 AN: 2106

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
PhyloP100		-0.99

Splicing

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

Other links and lift over

dbSNP: rs11122580; hg19: chr1-230851044;