chr1-230714053-A-G

Variant names:

• chr1-230714053-A-G
• rs2148582
• NM_001384479.1:c.-31+33T>C

Variant summary

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

The NM_001384479.1(AGT):​c.-31+33T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,938 control chromosomes in the GnomAD database, including 28,063 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 0.58 (28057 hom., cov: 31)
  • Exomes 𝑓: 0.57 (6 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0580
• Publications: 26 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384479.1. 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_001384479.1	MANE Select	c.-31+33T>C		intron	N/A	NP_001371408.1
	AGT	NM_001382817.3		c.-30-3200T>C		intron	N/A	NP_001369746.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.-31+33T>C		intron	N/A	ENSP00000355627.5
	AGT	ENST00000680041.1		c.-156+33T>C		intron	N/A	ENSP00000504866.1
	AGT	ENST00000681269.1		c.-30-3200T>C		intron	N/A	ENSP00000505985.1

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87899 AN: 151778 Hom.: 28002 Cov.: 31

Gnomad AFR AF: 0.829

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.639

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.833

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.575 AC: 23 AN: 40 Hom.: 6 Cov.: 0 AF XY: 0.625 AC XY: 20 AN XY: 32

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.575 AC: 23 AN: 40

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.579 AC: 88011 AN: 151898 Hom.: 28057 Cov.: 31 AF XY: 0.584 AC XY: 43337 AN XY: 74210

African (AFR) AF: 0.830 AC: 34396 AN: 41460

American (AMR) AF: 0.640 AC: 9768 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3464

East Asian (EAS) AF: 0.833 AC: 4275 AN: 5134

South Asian (SAS) AF: 0.622 AC: 2995 AN: 4812

European-Finnish (FIN) AF: 0.444 AC: 4684 AN: 10538

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.421 AC: 28599 AN: 67906

Other (OTH) AF: 0.566 AC: 1196 AN: 2114

Alfa AF: 0.479 Hom.: 24096

Bravo AF: 0.606

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.4
DANN	Benign	0.42
PhyloP100		-0.058
PromoterAI		0.063	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2148582; hg19: chr1-230849799;