1-230693019-G-T

Variant names:

• chr1-230693019-G-T
• rs2493125
• NM_007357.3:c.2116-273G>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007357.3(COG2):​c.2116-273G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.939 in 152,038 control chromosomes in the GnomAD database, including 67,122 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.94 (67122 hom., cov: 30)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.638
• Publications: 0 publications found

Genes affected

COG2 (HGNC:6546): (component of oligomeric golgi complex 2) This gene encodes a subunit of the conserved oligomeric Golgi complex that is required for maintaining normal structure and activity of the Golgi complex. The encoded protein specifically interacts with the USO1 vesicle docking protein and may be necessary for normal Golgi ribbon formation and trafficking of Golgi enzymes. Mutations of this gene are associated with abnormal glycosylation within the Golgi apparatus. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-230693019-G-T is Benign according to our data. Variant chr1-230693019-G-T is described in ClinVar as Benign. ClinVar VariationId is 1262085.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007357.3. 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
	COG2	NM_007357.3	MANE Select	c.2116-273G>T		intron	N/A	NP_031383.1	Q14746-1
	COG2	NM_001145036.2		c.2113-273G>T		intron	N/A	NP_001138508.1	Q14746-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG2	ENST00000366669.9	TSL:1 MANE Select	c.2116-273G>T		intron	N/A	ENSP00000355629.4	Q14746-1
	COG2	ENST00000366668.7	TSL:1	c.2113-273G>T		intron	N/A	ENSP00000355628.3	Q14746-2
	AGT	ENST00000680783.1		c.*1392C>A		3_prime_UTR	Exon 3 of 3	ENSP00000506329.1	A0A7P0TAP4

Frequencies

GnomAD3 genomes AF: 0.939 AC: 142621 AN: 151920 Hom.: 67070 Cov.: 30

Gnomad AFR AF: 0.884

Gnomad AMI AF: 0.980

Gnomad AMR AF: 0.943

Gnomad ASJ AF: 0.891

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.958

Gnomad FIN AF: 0.970

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.963

Gnomad OTH AF: 0.930

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

GnomAD4 genome AF: 0.939 AC: 142732 AN: 152038 Hom.: 67122 Cov.: 30 AF XY: 0.939 AC XY: 69802 AN XY: 74318

African (AFR) AF: 0.884 AC: 36626 AN: 41430

American (AMR) AF: 0.943 AC: 14410 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 3092 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5119 AN: 5154

South Asian (SAS) AF: 0.959 AC: 4609 AN: 4806

European-Finnish (FIN) AF: 0.970 AC: 10258 AN: 10580

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.963 AC: 65501 AN: 67996

Other (OTH) AF: 0.931 AC: 1971 AN: 2116

Alfa AF: 0.940 Hom.: 9531

Bravo AF: 0.935

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		0.64
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: rs2493125; hg19: chr1-230828765;