rs5051

Variant names:

• chr1-230714126-C-T
• rs5051
• ENST00000680041.1:c.-196G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-230714126-C-T
• chr1-230714126-C-A
• chr1-230714126-C-G

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.-30-3273G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,032 control chromosomes in the GnomAD database, including 28,516 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (28493 hom., cov: 31)
  • Exomes 𝑓: 0.48 (23 hom.)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.48
• Publications: 241 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=-0.77).
• BP6: Variant 1-230714126-C-T is Benign according to our data. Variant chr1-230714126-C-T is described in ClinVar as Benign. ClinVar VariationId is 296090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.835 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.-30-3273G>A		intron	N/A	NP_001369746.2	P01019
	AGT	NM_001384479.1	MANE Select	c.-71G>A		upstream_gene	N/A	NP_001371408.1	P01019

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AGT	ENST00000680041.1		c.-196G>A		5_prime_UTR	Exon 1 of 5	ENSP00000504866.1	P01019
	AGT	ENST00000679957.1		c.-71G>A		5_prime_UTR	Exon 1 of 5	ENSP00000506646.1	A0A7P0TBH1
	AGT	ENST00000679684.1		c.-71G>A		5_prime_UTR	Exon 1 of 5	ENSP00000505981.1	A0A7P0TA52

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88384 AN: 151728 Hom.: 28429 Cov.: 31

Gnomad AFR AF: 0.842

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.831

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.562

GnomAD4 exome AF: 0.478 AC: 89 AN: 186 Hom.: 23 Cov.: 0 AF XY: 0.481 AC XY: 74 AN XY: 154

African (AFR) AF: 1.00 AC: 6 AN: 6

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 1 AN: 4

East Asian (EAS) AF: 0.750 AC: 6 AN: 8

South Asian (SAS) AC: 0 AN: 0

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

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.443 AC: 70 AN: 158

Other (OTH) AF: 0.625 AC: 5 AN: 8

GnomAD4 genome AF: 0.583 AC: 88505 AN: 151846 Hom.: 28493 Cov.: 31 AF XY: 0.587 AC XY: 43579 AN XY: 74194

African (AFR) AF: 0.843 AC: 34955 AN: 41472

American (AMR) AF: 0.641 AC: 9783 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1556 AN: 3470

East Asian (EAS) AF: 0.831 AC: 4259 AN: 5128

South Asian (SAS) AF: 0.622 AC: 2980 AN: 4788

European-Finnish (FIN) AF: 0.443 AC: 4661 AN: 10514

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

European-Non Finnish (NFE) AF: 0.421 AC: 28577 AN: 67884

Other (OTH) AF: 0.566 AC: 1197 AN: 2114

Alfa AF: 0.488 Hom.: 54099

Bravo AF: 0.610

Asia WGS AF: 0.728 AC: 2530 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypertension, essential, susceptibility to (1)
-	-	1	Renal tubular dysgenesis (1)
-	-	1	Renal tubular dysgenesis of genetic origin (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.75
DANN	Benign	0.60
PhyloP100		-1.5
PromoterAI		-0.087	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs5051; hg19: chr1-230849872;