1-230719253-C-T

Variant names:

• chr1-230719253-C-T
• rs7555650
• NM_001382817.3:c.-30-8400G>A

Variant summary

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

The NM_001382817.3(AGT):​c.-30-8400G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 151,932 control chromosomes in the GnomAD database, including 3,497 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 0.19 (3497 hom., cov: 31)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0630
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001382817.3	c.-30-8400G>A		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.-30-8400G>A		intron_variant	Intron 1 of 4			ENSP00000505985.1
ENSG00000244137	ENST00000412344.1	n.381-8400G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28070 AN: 151818 Hom.: 3482 Cov.: 31

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0909

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.175

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

GnomAD4 genome AF: 0.185 AC: 28140 AN: 151932 Hom.: 3497 Cov.: 31 AF XY: 0.188 AC XY: 13927 AN XY: 74254

African (AFR) AF: 0.284 AC: 11744 AN: 41384

American (AMR) AF: 0.272 AC: 4149 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3468

East Asian (EAS) AF: 0.489 AC: 2521 AN: 5160

South Asian (SAS) AF: 0.210 AC: 1013 AN: 4816

European-Finnish (FIN) AF: 0.0909 AC: 959 AN: 10550

Middle Eastern (MID) AF: 0.0514 AC: 15 AN: 292

European-Non Finnish (NFE) AF: 0.104 AC: 7069 AN: 67982

Other (OTH) AF: 0.184 AC: 388 AN: 2112

Alfa AF: 0.133 Hom.: 1002

Bravo AF: 0.209

Asia WGS AF: 0.360 AC: 1252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.51
PhyloP100		-0.063

Splicing

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

Other links and lift over

dbSNP: rs7555650; hg19: chr1-230854999;