rs943580

Variant names:

• chr1-230701298-G-A
• rs943580
• ENST00000680783.1:c.830-6859C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-230701298-G-A
• chr1-230701298-G-C

Variant summary

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

The ENST00000680783.1(AGT):​c.830-6859C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,910 control chromosomes in the GnomAD database, including 16,256 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 0.42 (16256 hom., cov: 31)
• Consequence: AGT ENST00000680783.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.215
• Publications: 21 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000680783.1	c.830-6859C>T		intron_variant	Intron 2 of 2			ENSP00000506329.1
AGT	ENST00000679738.1	n.*786+1057C>T		intron_variant	Intron 5 of 6			ENSP00000505063.1
AGT	ENST00000679802.1	n.*1676+1057C>T		intron_variant	Intron 6 of 7			ENSP00000505184.1

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63684 AN: 151792 Hom.: 16259 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.509

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.158

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.560

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.419 AC: 63681 AN: 151910 Hom.: 16256 Cov.: 31 AF XY: 0.414 AC XY: 30716 AN XY: 74208

African (AFR) AF: 0.157 AC: 6507 AN: 41434

American (AMR) AF: 0.347 AC: 5283 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2037 AN: 3470

East Asian (EAS) AF: 0.158 AC: 820 AN: 5174

South Asian (SAS) AF: 0.381 AC: 1833 AN: 4810

European-Finnish (FIN) AF: 0.560 AC: 5891 AN: 10522

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39767 AN: 67956

Other (OTH) AF: 0.442 AC: 929 AN: 2104

Alfa AF: 0.511 Hom.: 46367

Bravo AF: 0.390

Asia WGS AF: 0.261 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.68
DANN	Benign	0.74
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs943580; hg19: chr1-230837044;