1-230710933-T-C

Variant names:

• chr1-230710933-T-C
• rs11122576
• NM_001384479.1:c.-30-80A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001384479.1(AGT):​c.-30-80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 1,517,660 control chromosomes in the GnomAD database, including 8,918 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.086 (852 hom., cov: 32)
  • Exomes 𝑓: 0.094 (8066 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0110
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-230710933-T-C is Benign according to our data. Variant chr1-230710933-T-C is described in ClinVar as Benign. ClinVar VariationId is 1247694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 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.-30-80A>G		intron	N/A	NP_001371408.1
	AGT	NM_001382817.3		c.-30-80A>G		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.-30-80A>G		intron	N/A	ENSP00000355627.5
	AGT	ENST00000680041.1		c.-110A>G		5_prime_UTR	Exon 2 of 5	ENSP00000504866.1
	AGT	ENST00000681269.1		c.-30-80A>G		intron	N/A	ENSP00000505985.1

Frequencies

GnomAD3 genomes AF: 0.0860 AC: 13088 AN: 152170 Hom.: 854 Cov.: 32

Gnomad AFR AF: 0.0474

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0842

Gnomad OTH AF: 0.0783

GnomAD4 exome AF: 0.0943 AC: 128724 AN: 1365372 Hom.: 8066 AF XY: 0.0940 AC XY: 64250 AN XY: 683284

African (AFR) AF: 0.0448 AC: 1418 AN: 31632

American (AMR) AF: 0.212 AC: 9224 AN: 43554

Ashkenazi Jewish (ASJ) AF: 0.0336 AC: 859 AN: 25530

East Asian (EAS) AF: 0.339 AC: 13308 AN: 39200

South Asian (SAS) AF: 0.0998 AC: 8317 AN: 83368

European-Finnish (FIN) AF: 0.0544 AC: 2111 AN: 38780

Middle Eastern (MID) AF: 0.0475 AC: 220 AN: 4628

European-Non Finnish (NFE) AF: 0.0843 AC: 87785 AN: 1041138

Other (OTH) AF: 0.0953 AC: 5482 AN: 57542

GnomAD4 genome AF: 0.0860 AC: 13090 AN: 152288 Hom.: 852 Cov.: 32 AF XY: 0.0877 AC XY: 6531 AN XY: 74472

African (AFR) AF: 0.0474 AC: 1970 AN: 41570

American (AMR) AF: 0.146 AC: 2230 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3470

East Asian (EAS) AF: 0.352 AC: 1819 AN: 5170

South Asian (SAS) AF: 0.111 AC: 533 AN: 4822

European-Finnish (FIN) AF: 0.0423 AC: 449 AN: 10626

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0841 AC: 5722 AN: 68000

Other (OTH) AF: 0.0789 AC: 167 AN: 2116

Alfa AF: 0.0888 Hom.: 3035

Bravo AF: 0.0943

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.2
DANN	Benign	0.50
PhyloP100		0.011
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: rs11122576; hg19: chr1-230846679; COSMIC: COSV64185498;