rs3757713

Variant names:

• chr7-107402305-A-C
• rs3757713
• NM_006348.5:c.669+10197T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-107402305-A-C
• chr7-107402305-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006348.5(COG5):​c.669+10197T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,136 control chromosomes in the GnomAD database, including 2,291 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2291 hom., cov: 32)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 6 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG5	NM_006348.5	c.669+10197T>G		intron_variant	Intron 7 of 21	ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9	c.669+10197T>G		intron_variant	Intron 7 of 21	1	NM_006348.5	ENSP00000297135.4

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23651 AN: 152018 Hom.: 2296 Cov.: 32

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.168

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.215

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.155 AC: 23641 AN: 152136 Hom.: 2291 Cov.: 32 AF XY: 0.153 AC XY: 11412 AN XY: 74378

African (AFR) AF: 0.0425 AC: 1766 AN: 41542

American (AMR) AF: 0.168 AC: 2566 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 779 AN: 3466

East Asian (EAS) AF: 0.136 AC: 706 AN: 5178

South Asian (SAS) AF: 0.178 AC: 859 AN: 4820

European-Finnish (FIN) AF: 0.167 AC: 1766 AN: 10574

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.215 AC: 14583 AN: 67952

Other (OTH) AF: 0.164 AC: 348 AN: 2116

Alfa AF: 0.176 Hom.: 449

Bravo AF: 0.153

Asia WGS AF: 0.171 AC: 596 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.62
PhyloP100		0.12
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: rs3757713; hg19: chr7-107042750;