rs3827749

Variant names:

• chr1-230705813-G-A
• rs3827749
• NM_001384479.1:c.1097+120C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-230705813-G-A
• chr1-230705813-G-T

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.1097+120C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,347,132 control chromosomes in the GnomAD database, including 36,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7050 hom., cov: 33)
  • Exomes 𝑓: 0.21 (29770 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.87
• Publications: 10 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=-0.92).
• BP6: Variant 1-230705813-G-A is Benign according to our data. Variant chr1-230705813-G-A is described in ClinVar as Benign. ClinVar VariationId is 1276076.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.1097+120C>T		intron_variant	Intron 3 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.1097+120C>T		intron_variant	Intron 3 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.1097+120C>T		intron_variant	Intron 3 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.286 AC: 43488 AN: 151926 Hom.: 7024 Cov.: 33

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.287

GnomAD4 exome AF: 0.211 AC: 252597 AN: 1195088 Hom.: 29770 AF XY: 0.211 AC XY: 126925 AN XY: 600386

African (AFR) AF: 0.447 AC: 12408 AN: 27782

American (AMR) AF: 0.405 AC: 16712 AN: 41256

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 4148 AN: 22478

East Asian (EAS) AF: 0.321 AC: 12172 AN: 37950

South Asian (SAS) AF: 0.265 AC: 20233 AN: 76462

European-Finnish (FIN) AF: 0.254 AC: 12947 AN: 50920

Middle Eastern (MID) AF: 0.226 AC: 886 AN: 3920

European-Non Finnish (NFE) AF: 0.183 AC: 161538 AN: 883306

Other (OTH) AF: 0.226 AC: 11553 AN: 51014

GnomAD4 genome AF: 0.286 AC: 43555 AN: 152044 Hom.: 7050 Cov.: 33 AF XY: 0.291 AC XY: 21640 AN XY: 74292

African (AFR) AF: 0.437 AC: 18109 AN: 41438

American (AMR) AF: 0.340 AC: 5205 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.188 AC: 651 AN: 3472

East Asian (EAS) AF: 0.303 AC: 1561 AN: 5146

South Asian (SAS) AF: 0.283 AC: 1364 AN: 4820

European-Finnish (FIN) AF: 0.276 AC: 2921 AN: 10594

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

European-Non Finnish (NFE) AF: 0.188 AC: 12800 AN: 67966

Other (OTH) AF: 0.292 AC: 616 AN: 2112

Alfa AF: 0.256 Hom.: 693

Bravo AF: 0.301

Asia WGS AF: 0.299 AC: 1038 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0070
DANN	Benign	0.33
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs3827749; hg19: chr1-230841559; COSMIC: COSV64184823; COSMIC: COSV64184823;