NM_001382817.3:c.-31+14161G>C

Variant names:

• chr1-230731354-C-G
• rs11122587
• NM_001382817.3:c.-31+14161G>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.-31+14161G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,142 control chromosomes in the GnomAD database, including 8,396 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 0.31 (8396 hom., cov: 32)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.196
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382817.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001382817.3		c.-31+14161G>C		intron	N/A	NP_001369746.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000681269.1		c.-31+14161G>C		intron	N/A	ENSP00000505985.1
	ENSG00000244137	ENST00000412344.1	TSL:3	n.381-20501G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46722 AN: 152024 Hom.: 8350 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.665

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.308 AC: 46827 AN: 152142 Hom.: 8396 Cov.: 32 AF XY: 0.313 AC XY: 23266 AN XY: 74392

African (AFR) AF: 0.421 AC: 17453 AN: 41478

American (AMR) AF: 0.388 AC: 5923 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.665 AC: 3433 AN: 5162

South Asian (SAS) AF: 0.414 AC: 2001 AN: 4828

European-Finnish (FIN) AF: 0.185 AC: 1957 AN: 10602

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14717 AN: 68008

Other (OTH) AF: 0.300 AC: 634 AN: 2114

Alfa AF: 0.270 Hom.: 745

Bravo AF: 0.328

Asia WGS AF: 0.549 AC: 1910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.45
PhyloP100		0.20

Splicing

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

Other links and lift over

dbSNP: rs11122587; hg19: chr1-230867100;