7-107248422-G-A

Position:

chr7-107248422-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_006348.5(COG5):c.1827C>T(p.Ile609Ile) variant causes a synonymous change. The variant allele was found at a frequency of 0.0377 in 1,610,482 control chromosomes in the GnomAD database, including 1,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 128 hom., cov: 31)

Exomes 𝑓: 0.038 ( 1197 hom. )

Consequence

COG5
NM_006348.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.61

Variant links:

Genes affected

COG5 (HGNC:14857): (component of oligomeric golgi complex 5) 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. The encoded protein is organized with conserved oligomeric Golgi complex components 6, 7 and 8 into a sub-complex referred to as lobe B. Alternative splicing results in multiple transcript variants. Mutations in this gene result in congenital disorder of glycosylation type 2I.[provided by RefSeq, Jan 2011]

COG5 links:

COG5 (HGNC:):

COG5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant 7-107248422-G-A is Benign according to our data. Variant chr7-107248422-G-A is described in ClinVar as [Benign]. Clinvar id is 358456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-107248422-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.032 (4846/151620) while in subpopulation NFE AF= 0.0465 (3160/67940). AF 95% confidence interval is 0.0452. There are 128 homozygotes in gnomad4. There are 2321 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 128 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG5	NM_006348.5 linkuse as main transcript	c.1827C>T	p.Ile609Ile	synonymous_variant	17/22	ENST00000297135.9	NP_006339.4	Q9UP83

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9 linkuse as main transcript	c.1827C>T	p.Ile609Ile	synonymous_variant	17/22	1	NM_006348.5	ENSP00000297135.4		Q9UP83

Frequencies

GnomAD3 genomes

AF:

0.0320

AC:

4846

AN:

151504

Hom.:

128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00970

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0318

Gnomad ASJ

AF:

0.0577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00668

Gnomad FIN

AF:

0.0454

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0465

Gnomad OTH

AF:

0.0380

GnomAD3 exomes

AF:

0.0322

AC:

8096

AN:

251292

Hom.:

172

AF XY:

0.0320

AC XY:

4340

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.00849

Gnomad AMR exome

AF:

0.0225

Gnomad ASJ exome

AF:

0.0561

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00719

Gnomad FIN exome

AF:

0.0432

Gnomad NFE exome

AF:

0.0461

Gnomad OTH exome

AF:

0.0364

GnomAD4 exome

AF:

0.0383

AC:

55895

AN:

1458862

Hom.:

1197

Cov.:

AF XY:

0.0376

AC XY:

27289

AN XY:

725866

show subpopulations

Gnomad4 AFR exome

AF:

0.00751

Gnomad4 AMR exome

AF:

0.0235

Gnomad4 ASJ exome

AF:

0.0571

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00718

Gnomad4 FIN exome

AF:

0.0425

Gnomad4 NFE exome

AF:

0.0433

Gnomad4 OTH exome

AF:

0.0346

GnomAD4 genome

AF:

0.0320

AC:

4846

AN:

151620

Hom.:

128

Cov.:

AF XY:

0.0313

AC XY:

2321

AN XY:

74080

show subpopulations

Gnomad4 AFR

AF:

0.00968

Gnomad4 AMR

AF:

0.0317

Gnomad4 ASJ

AF:

0.0577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00690

Gnomad4 FIN

AF:

0.0454

Gnomad4 NFE

AF:

0.0465

Gnomad4 OTH

AF:

0.0376

Alfa

AF:

0.0437

Hom.:

Bravo

AF:

0.0297

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0415

EpiControl

AF:

0.0443

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

COG5-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 25, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided

Benign:1

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

-0.35

CADD

Benign

8.4

DANN

Benign

0.73

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over