rs3789679

Variant names:

• chr1-230713948-G-A
• rs3789679
• NM_001384479.1:c.-31+138C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-230713948-G-A
• chr1-230713948-G-C
• chr1-230713948-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384479.1(AGT):​c.-31+138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 152,200 control chromosomes in the GnomAD database, including 1,234 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1234 hom., cov: 32)
  • Exomes 𝑓: 0.066 (0 hom.)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.290
• Publications: 16 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)

ENSG00000244137 (HGNC:58238):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-31+138C>T		intron_variant	Intron 1 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-3095C>T		intron_variant	Intron 1 of 4		NP_001369746.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AGT	ENST00000366667.6	c.-31+138C>T		intron_variant	Intron 1 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16856 AN: 152006 Hom.: 1234 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0357

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0418

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.0979

GnomAD4 exome AF: 0.0658 AC: 5 AN: 76 Hom.: 0 AF XY: 0.0667 AC XY: 4 AN XY: 60

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

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

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0758 AC: 5 AN: 66

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.111 AC: 16866 AN: 152124 Hom.: 1234 Cov.: 32 AF XY: 0.111 AC XY: 8251 AN XY: 74382

African (AFR) AF: 0.137 AC: 5694 AN: 41494

American (AMR) AF: 0.157 AC: 2400 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0357 AC: 124 AN: 3472

East Asian (EAS) AF: 0.352 AC: 1811 AN: 5150

South Asian (SAS) AF: 0.105 AC: 506 AN: 4812

European-Finnish (FIN) AF: 0.0418 AC: 444 AN: 10610

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0827 AC: 5624 AN: 67980

Other (OTH) AF: 0.0983 AC: 207 AN: 2106

Alfa AF: 0.0567 Hom.: 75

Bravo AF: 0.124

Asia WGS AF: 0.218 AC: 756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.7
DANN	Benign	0.74
PhyloP100		-0.29
PromoterAI		-0.039	Neutral
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: rs3789679; hg19: chr1-230849694;