rs1078499

Variant names:

• chr1-230713350-A-G
• rs1078499
• NM_001384479.1:c.-31+736T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-230713350-A-G
• chr1-230713350-A-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+736T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,022 control chromosomes in the GnomAD database, including 7,233 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 0.30 (7233 hom., cov: 32)
• Consequence: AGT NM_001384479.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0500
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AGT	NM_001384479.1	c.-31+736T>C		intron_variant	Intron 1 of 4	ENST00000366667.6	NP_001371408.1
AGT	NM_001382817.3	c.-30-2497T>C		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+736T>C		intron_variant	Intron 1 of 4	1	NM_001384479.1	ENSP00000355627.5

Frequencies

GnomAD3 genomes AF: 0.298 AC: 45334 AN: 151904 Hom.: 7216 Cov.: 32

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.313

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45391 AN: 152022 Hom.: 7233 Cov.: 32 AF XY: 0.303 AC XY: 22481 AN XY: 74280

African (AFR) AF: 0.403 AC: 16727 AN: 41464

American (AMR) AF: 0.343 AC: 5233 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1067 AN: 3468

East Asian (EAS) AF: 0.305 AC: 1572 AN: 5156

South Asian (SAS) AF: 0.306 AC: 1475 AN: 4818

European-Finnish (FIN) AF: 0.294 AC: 3110 AN: 10562

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15174 AN: 67966

Other (OTH) AF: 0.312 AC: 659 AN: 2110

Alfa AF: 0.296 Hom.: 1025

Bravo AF: 0.309

Asia WGS AF: 0.313 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.64
PhyloP100		0.050
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1078499; hg19: chr1-230849096;