rs3815148

Variant names:

• chr7-107297975-A-C
• rs3815148
• NM_006348.5:c.1313+167T>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006348.5(COG5):​c.1313+167T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 152,114 control chromosomes in the GnomAD database, including 3,184 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.20 (3184 hom., cov: 31)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.900
• Publications: 43 publications found

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 Gene-Disease associations (from GenCC):

• COG5-congenital disorder of glycosylation

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine, Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 7-107297975-A-C is Benign according to our data. Variant chr7-107297975-A-C is described in ClinVar as Benign. ClinVar VariationId is 1237233.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG5	NM_006348.5	c.1313+167T>G		intron_variant	Intron 12 of 21	ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9	c.1313+167T>G		intron_variant	Intron 12 of 21	1	NM_006348.5	ENSP00000297135.4
COG5	ENST00000347053.8	c.1313+167T>G		intron_variant	Intron 12 of 20	1		ENSP00000334703.3
COG5	ENST00000393603.7	c.1313+167T>G		intron_variant	Intron 12 of 20	1		ENSP00000377228.3

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30541 AN: 151996 Hom.: 3184 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.184

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.199

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

GnomAD4 genome AF: 0.201 AC: 30562 AN: 152114 Hom.: 3184 Cov.: 31 AF XY: 0.197 AC XY: 14627 AN XY: 74360

African (AFR) AF: 0.198 AC: 8205 AN: 41500

American (AMR) AF: 0.183 AC: 2805 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 799 AN: 3470

East Asian (EAS) AF: 0.139 AC: 721 AN: 5180

South Asian (SAS) AF: 0.177 AC: 854 AN: 4820

European-Finnish (FIN) AF: 0.169 AC: 1785 AN: 10560

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14706 AN: 67974

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.212 Hom.: 8424

Bravo AF: 0.205

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 05, 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	-0.95
CADD	Benign	2.8
DANN	Benign	0.71
PhyloP100		-0.90
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

Other links and lift over

dbSNP: rs3815148; hg19: chr7-106938420;