1-230693241-C-A

Position:

• chr1-230693241-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_007357.3(COG2):​c.2116-51C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 1,029,706 control chromosomes in the GnomAD database, including 85,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.32 (9579 hom., cov: 33)
  • Exomes 𝑓: 0.40 (76288 hom.)
• Consequence: COG2 NM_007357.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.275

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-230693241-C-A is Benign according to our data. Variant chr1-230693241-C-A is described in ClinVar as [Benign]. Clinvar id is 1177936.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG2	NM_007357.3	c.2116-51C>A		intron_variant		ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.2113-51C>A		intron_variant			NP_001138508.1
COG2	XM_047449445.1	c.1777-51C>A		intron_variant			XP_047305401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.2116-51C>A		intron_variant		1	NM_007357.3	ENSP00000355629.4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49388 AN: 151904 Hom.: 9577 Cov.: 33

Gnomad AFR AF: 0.142

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.335

GnomAD3 exomes AF: 0.346 AC: 81995 AN: 236714 Hom.: 16258 AF XY: 0.359 AC XY: 45997 AN XY: 128136

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.179

Gnomad ASJ exome AF: 0.413

Gnomad EAS exome AF: 0.113

Gnomad SAS exome AF: 0.339

Gnomad FIN exome AF: 0.431

Gnomad NFE exome AF: 0.441

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.401 AC: 351606 AN: 877684 Hom.: 76288 Cov.: 11 AF XY: 0.401 AC XY: 183880 AN XY: 458858

Gnomad4 AFR exome AF: 0.135

Gnomad4 AMR exome AF: 0.189

Gnomad4 ASJ exome AF: 0.414

Gnomad4 EAS exome AF: 0.126

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.441

Gnomad4 NFE exome AF: 0.447

Gnomad4 OTH exome AF: 0.381

GnomAD4 genome AF: 0.325 AC: 49396 AN: 152022 Hom.: 9579 Cov.: 33 AF XY: 0.323 AC XY: 23969 AN XY: 74282

Gnomad4 AFR AF: 0.142

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.420

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.429

Gnomad4 NFE AF: 0.442

Gnomad4 OTH AF: 0.332

Alfa AF: 0.376 Hom.: 2147

Bravo AF: 0.302

Asia WGS AF: 0.218 AC: 761 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 27, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.91
DANN	Benign	0.32

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: rs2478534; hg19: chr1-230828987; COSMIC: COSV64186826; COSMIC: COSV64186826;