rs7079

Variant names:

• chr1-230702585-G-T
• rs7079
• NM_001384479.1:c.*556C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-230702585-G-T
• chr1-230702585-G-A
• chr1-230702585-G-C

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.*556C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 157,228 control chromosomes in the GnomAD database, including 5,858 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: 0.26 (216 hom.)
• Consequence: AGT NM_001384479.1 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0350
• Publications: 62 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=-0.83).
• BP6: Variant 1-230702585-G-T is Benign according to our data. Variant chr1-230702585-G-T is described in ClinVar as Benign. ClinVar VariationId is 296063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001384479.1	MANE Select	c.*556C>A		3_prime_UTR	Exon 5 of 5	NP_001371408.1	P01019
	AGT	NM_001382817.3		c.*556C>A		3_prime_UTR	Exon 5 of 5	NP_001369746.2	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000366667.6	TSL:1 MANE Select	c.*556C>A		3_prime_UTR	Exon 5 of 5	ENSP00000355627.5	P01019
	AGT	ENST00000680041.1		c.*556C>A		3_prime_UTR	Exon 5 of 5	ENSP00000504866.1	P01019
	AGT	ENST00000681269.1		c.*556C>A		3_prime_UTR	Exon 5 of 5	ENSP00000505985.1	P01019

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38192 AN: 151958 Hom.: 5648 Cov.: 33

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.338

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.128

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.328

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.261 AC: 1344 AN: 5152 Hom.: 216 Cov.: 0 AF XY: 0.250 AC XY: 653 AN XY: 2608

African (AFR) AF: 0.00 AC: 0 AN: 20

American (AMR) AF: 0.161 AC: 229 AN: 1424

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 3 AN: 8

East Asian (EAS) AF: 0.0776 AC: 18 AN: 232

South Asian (SAS) AF: 0.266 AC: 130 AN: 488

European-Finnish (FIN) AF: 0.300 AC: 6 AN: 20

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.325 AC: 907 AN: 2788

Other (OTH) AF: 0.304 AC: 51 AN: 168

GnomAD4 genome AF: 0.251 AC: 38184 AN: 152076 Hom.: 5642 Cov.: 33 AF XY: 0.252 AC XY: 18731 AN XY: 74332

African (AFR) AF: 0.107 AC: 4439 AN: 41508

American (AMR) AF: 0.201 AC: 3067 AN: 15272

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

East Asian (EAS) AF: 0.129 AC: 664 AN: 5166

South Asian (SAS) AF: 0.296 AC: 1432 AN: 4830

European-Finnish (FIN) AF: 0.367 AC: 3880 AN: 10560

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

European-Non Finnish (NFE) AF: 0.328 AC: 22307 AN: 67956

Other (OTH) AF: 0.260 AC: 549 AN: 2110

Alfa AF: 0.296 Hom.: 23075

Bravo AF: 0.230

Asia WGS AF: 0.197 AC: 690 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Renal tubular dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.55
PhyloP100		0.035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs7079; hg19: chr1-230838331;