1-230693127-A-G

Position:

• chr1-230693127-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007357.3(COG2):​c.2116-165A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,036 control chromosomes in the GnomAD database, including 5,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (5344 hom., cov: 32)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.929

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-230693127-A-G is Benign according to our data. Variant chr1-230693127-A-G is described in ClinVar as [Benign]. Clinvar id is 1238822.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.2116-165A>G		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.2113-165A>G		intron_variant			NP_001138508.1
COG2	XM_047449445.1	c.1777-165A>G		intron_variant			XP_047305401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.2116-165A>G		intron_variant		1	NM_007357.3	ENSP00000355629.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37910 AN: 151918 Hom.: 5337 Cov.: 32

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.360

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.584

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.237

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

GnomAD4 genome AF: 0.250 AC: 37949 AN: 152036 Hom.: 5344 Cov.: 32 AF XY: 0.257 AC XY: 19129 AN XY: 74302

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.371

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.582

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.288

Gnomad4 NFE AF: 0.213

Gnomad4 OTH AF: 0.245

Alfa AF: 0.225 Hom.: 8550

Bravo AF: 0.260

Asia WGS AF: 0.442 AC: 1536 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.7
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs3789662; hg19: chr1-230828873; COSMIC: COSV64185852; COSMIC: COSV64185852;