1-230714337-C-T

Variant names:

• chr1-230714337-C-T
• rs5049
• ENST00000679957.1:c.-282G>A

Variant summary

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

The NM_001382817.3(AGT):​c.-30-3484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 152,278 control chromosomes in the GnomAD database, including 2,314 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2312 hom., cov: 32)
  • Exomes 𝑓: 0.16 (2 hom.)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.49
• Publications: 74 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)

CAPN9-AS1 (HGNC:58238):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-230714337-C-T is Benign according to our data. Variant chr1-230714337-C-T is described in ClinVar as Benign. ClinVar VariationId is 296097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	NM_001382817.3		c.-30-3484G>A		intron	N/A	NP_001369746.2	P01019
	AGT	NM_001384479.1	MANE Select	c.-282G>A		upstream_gene	N/A	NP_001371408.1	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000679957.1		c.-282G>A		5_prime_UTR	Exon 1 of 5	ENSP00000506646.1	A0A7P0TBH1
	AGT	ENST00000679684.1		c.-282G>A		5_prime_UTR	Exon 1 of 5	ENSP00000505981.1	A0A7P0TA52
	AGT	ENST00000680783.1		c.-282G>A		5_prime_UTR	Exon 1 of 3	ENSP00000506329.1	A0A7P0TAP4

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24448 AN: 152014 Hom.: 2302 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0636

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.141

GnomAD4 exome AF: 0.158 AC: 23 AN: 146 Hom.: 2 Cov.: 0 AF XY: 0.196 AC XY: 20 AN XY: 102

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.161 AC: 19 AN: 118

Other (OTH) AF: 0.250 AC: 3 AN: 12

GnomAD4 genome AF: 0.161 AC: 24487 AN: 152132 Hom.: 2312 Cov.: 32 AF XY: 0.162 AC XY: 12045 AN XY: 74372

African (AFR) AF: 0.266 AC: 11026 AN: 41466

American (AMR) AF: 0.131 AC: 1998 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.174 AC: 900 AN: 5168

South Asian (SAS) AF: 0.205 AC: 990 AN: 4818

European-Finnish (FIN) AF: 0.107 AC: 1132 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7736 AN: 68008

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.133 Hom.: 2206

Bravo AF: 0.163

Asia WGS AF: 0.195 AC: 679 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Renal tubular dysgenesis (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.79
DANN	Benign	0.92
PhyloP100		-1.5
PromoterAI		0.036	Neutral

Splicing

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

Other links and lift over

dbSNP: rs5049; hg19: chr1-230850083;