1-230693241-C-A

Variant names:

• chr1-230693241-C-A
• rs2478534
• NM_007357.3:c.2116-51C>A

Variant summary

Our verdict is Benign. The variant received -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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
COG2	NM_007357.3	c.2116-51C>A		intron_variant	Intron 17 of 17	ENST00000366669.9	NP_031383.1
COG2	NM_001145036.2	c.2113-51C>A		intron_variant	Intron 17 of 17		NP_001138508.1
COG2	XM_047449445.1	c.1777-51C>A		intron_variant	Intron 15 of 15		XP_047305401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG2	ENST00000366669.9	c.2116-51C>A		intron_variant	Intron 17 of 17	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

GnomAD2 exomes AF: 0.346 AC: 81995 AN: 236714 AF XY: 0.359

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 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 AC: 2965 AN: 21938

Gnomad4 AMR exome AF: 0.189 AC: 7786 AN: 41134

Gnomad4 ASJ exome AF: 0.414 AC: 9189 AN: 22188

Gnomad4 EAS exome AF: 0.126 AC: 4601 AN: 36476

Gnomad4 SAS exome AF: 0.342 AC: 24412 AN: 71334

Gnomad4 FIN exome AF: 0.441 AC: 23244 AN: 52754

Gnomad4 NFE exome AF: 0.447 AC: 262112 AN: 586448

Gnomad4 Remaining exome AF: 0.381 AC: 15549 AN: 40824

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 AC: 0.14172 AN: 0.14172

Gnomad4 AMR AF: 0.267 AC: 0.266614 AN: 0.266614

Gnomad4 ASJ AF: 0.420 AC: 0.419597 AN: 0.419597

Gnomad4 EAS AF: 0.124 AC: 0.12355 AN: 0.12355

Gnomad4 SAS AF: 0.338 AC: 0.338394 AN: 0.338394

Gnomad4 FIN AF: 0.429 AC: 0.428883 AN: 0.428883

Gnomad4 NFE AF: 0.442 AC: 0.441685 AN: 0.441685

Gnomad4 OTH AF: 0.332 AC: 0.332227 AN: 0.332227

Alfa AF: 0.379 Hom.: 3815

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

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

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