rs1026129

Variant names:

• chr17-73200856-G-A
• rs1026129
• NM_018714.3:c.1281+80G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-73200856-G-A
• chr17-73200856-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018714.3(COG1):​c.1281+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.525 in 1,298,304 control chromosomes in the GnomAD database, including 180,217 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20173 hom., cov: 31)
  • Exomes 𝑓: 0.53 (160044 hom.)
• Consequence: COG1 NM_018714.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.01
• Publications: 13 publications found

Genes affected

COG1 (HGNC:6545): (component of oligomeric golgi complex 1) The protein encoded by this gene is one of eight proteins (Cog1-8) which form a Golgi-localized complex (COG) required for normal Golgi morphology and function. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]

COG1 Gene-Disease associations (from GenCC):

• COG1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 17-73200856-G-A is Benign according to our data. Variant chr17-73200856-G-A is described in ClinVar as Benign. ClinVar VariationId is 1249591.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG1	NM_018714.3	c.1281+80G>A		intron_variant	Intron 6 of 13	ENST00000299886.9	NP_061184.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG1	ENST00000299886.9	c.1281+80G>A		intron_variant	Intron 6 of 13	1	NM_018714.3	ENSP00000299886.4
COG1	ENST00000438720.7	c.1278+80G>A		intron_variant	Intron 6 of 12	1		ENSP00000400111.3

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78007 AN: 151738 Hom.: 20159 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.444

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.509

GnomAD4 exome AF: 0.526 AC: 603139 AN: 1146448 Hom.: 160044 AF XY: 0.525 AC XY: 306835 AN XY: 584912

African (AFR) AF: 0.502 AC: 13648 AN: 27192

American (AMR) AF: 0.532 AC: 22841 AN: 42974

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 10837 AN: 24174

East Asian (EAS) AF: 0.622 AC: 23794 AN: 38262

South Asian (SAS) AF: 0.477 AC: 37539 AN: 78686

European-Finnish (FIN) AF: 0.478 AC: 24354 AN: 50922

Middle Eastern (MID) AF: 0.558 AC: 2322 AN: 4158

European-Non Finnish (NFE) AF: 0.532 AC: 441856 AN: 830080

Other (OTH) AF: 0.519 AC: 25948 AN: 50000

GnomAD4 genome AF: 0.514 AC: 78074 AN: 151856 Hom.: 20173 Cov.: 31 AF XY: 0.511 AC XY: 37931 AN XY: 74220

African (AFR) AF: 0.502 AC: 20773 AN: 41396

American (AMR) AF: 0.492 AC: 7504 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 1540 AN: 3472

East Asian (EAS) AF: 0.599 AC: 3086 AN: 5152

South Asian (SAS) AF: 0.470 AC: 2263 AN: 4818

European-Finnish (FIN) AF: 0.481 AC: 5075 AN: 10540

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36142 AN: 67926

Other (OTH) AF: 0.513 AC: 1079 AN: 2104

Alfa AF: 0.507 Hom.: 3781

Bravo AF: 0.520

Asia WGS AF: 0.527 AC: 1828 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.10
DANN	Benign	0.66
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1026129; hg19: chr17-71196995;