chr1-230714140-T-G

Variant names:

• chr1-230714140-T-G
• rs5050
• ENST00000680041.1:c.-210A>C

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.-30-3287A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,786 control chromosomes in the GnomAD database, including 2,246 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2240 hom., cov: 31)
  • Exomes 𝑓: 0.20 (6 hom.)
• Consequence: AGT NM_001382817.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.202
• Publications: 150 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 1-230714140-T-G is Benign according to our data. Variant chr1-230714140-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 296092.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.18 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.-30-3287A>C		intron	N/A	NP_001369746.2	P01019
	AGT	NM_001384479.1	MANE Select	c.-85A>C		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.-210A>C		5_prime_UTR	Exon 1 of 5	ENSP00000504866.1	P01019
	AGT	ENST00000679957.1		c.-85A>C		5_prime_UTR	Exon 1 of 5	ENSP00000506646.1	A0A7P0TBH1
	AGT	ENST00000679684.1		c.-85A>C		5_prime_UTR	Exon 1 of 5	ENSP00000505981.1	A0A7P0TA52

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25626 AN: 151492 Hom.: 2239 Cov.: 31

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.180

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.177

GnomAD4 exome AF: 0.198 AC: 34 AN: 172 Hom.: 6 Cov.: 0 AF XY: 0.200 AC XY: 28 AN XY: 140

African (AFR) AF: 0.00 AC: 0 AN: 6

American (AMR) AC: 0 AN: 0

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

East Asian (EAS) AF: 0.167 AC: 1 AN: 6

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.209 AC: 31 AN: 148

Other (OTH) AF: 0.167 AC: 1 AN: 6

GnomAD4 genome AF: 0.169 AC: 25633 AN: 151614 Hom.: 2240 Cov.: 31 AF XY: 0.171 AC XY: 12679 AN XY: 74062

African (AFR) AF: 0.147 AC: 6107 AN: 41456

American (AMR) AF: 0.186 AC: 2833 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.180 AC: 620 AN: 3452

East Asian (EAS) AF: 0.168 AC: 858 AN: 5116

South Asian (SAS) AF: 0.182 AC: 871 AN: 4776

European-Finnish (FIN) AF: 0.216 AC: 2256 AN: 10448

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.169 AC: 11426 AN: 67810

Other (OTH) AF: 0.176 AC: 371 AN: 2110

Alfa AF: 0.127 Hom.: 396

Bravo AF: 0.166

ClinVar

ClinVar submissions

Significance: Benign/Likely 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	-0.77
CADD	Benign	5.6
DANN	Benign	0.74
PhyloP100		-0.20
PromoterAI		0.53	Over-expression
Mutation Taster		=291/9	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: rs5050; hg19: chr1-230849886;