1-230702512-G-A

Variant names:

• chr1-230702512-G-A
• rs2067853
• ENST00000679738.1:n.*629C>T

Variant summary

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

The ENST00000679738.1(AGT):​n.*629C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 155,574 control chromosomes in the GnomAD database, including 5,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5642 hom., cov: 33)
  • Exomes 𝑓: 0.25 (134 hom.)
• Consequence: AGT ENST00000679738.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.487
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-230702512-G-A is Benign according to our data. Variant chr1-230702512-G-A is described in ClinVar as Benign. ClinVar VariationId is 368868.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000679738.1. 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.*629C>T		downstream_gene	N/A	NP_001371408.1
	AGT	NM_001382817.3		c.*629C>T		downstream_gene	N/A	NP_001369746.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000679738.1		n.*629C>T		non_coding_transcript_exon	Exon 5 of 7	ENSP00000505063.1
	AGT	ENST00000679802.1		n.*1519C>T		non_coding_transcript_exon	Exon 6 of 8	ENSP00000505184.1
	AGT	ENST00000679854.1		n.6365C>T		non_coding_transcript_exon	Exon 4 of 6

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38199 AN: 152034 Hom.: 5648 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.264

GnomAD4 exome AF: 0.250 AC: 857 AN: 3422 Hom.: 134 Cov.: 0 AF XY: 0.247 AC XY: 427 AN XY: 1726

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.141 AC: 133 AN: 944

Ashkenazi Jewish (ASJ) AF: 0.833 AC: 5 AN: 6

East Asian (EAS) AF: 0.0854 AC: 7 AN: 82

South Asian (SAS) AF: 0.245 AC: 52 AN: 212

European-Finnish (FIN) AF: 0.375 AC: 3 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.307 AC: 629 AN: 2048

Other (OTH) AF: 0.246 AC: 28 AN: 114

GnomAD4 genome AF: 0.251 AC: 38191 AN: 152152 Hom.: 5642 Cov.: 33 AF XY: 0.252 AC XY: 18735 AN XY: 74384

African (AFR) AF: 0.107 AC: 4445 AN: 41546

American (AMR) AF: 0.200 AC: 3064 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1430 AN: 3470

East Asian (EAS) AF: 0.129 AC: 669 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1430 AN: 4822

European-Finnish (FIN) AF: 0.368 AC: 3884 AN: 10566

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.328 AC: 22299 AN: 67978

Other (OTH) AF: 0.261 AC: 552 AN: 2112

Alfa AF: 0.288 Hom.: 17887

Bravo AF: 0.230

Asia WGS AF: 0.197 AC: 690 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Renal tubular dysgenesis Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

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	-0.80
CADD	Benign	4.8
DANN	Benign	0.72
PhyloP100		0.49

Splicing

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

Other links and lift over

dbSNP: rs2067853; hg19: chr1-230838258;