chr7-107498830-A-C

Variant names:

• chr7-107498830-A-C
• rs12535761
• NM_006348.5:c.538+28407T>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.538+28407T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 152,200 control chromosomes in the GnomAD database, including 1,503 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 0.13 (1503 hom., cov: 32)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0990
• Publications: 3 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 = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG5	NM_006348.5	c.538+28407T>G		intron_variant	Intron 6 of 21	ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9	c.538+28407T>G		intron_variant	Intron 6 of 21	1	NM_006348.5	ENSP00000297135.4
COG5	ENST00000347053.8	c.538+28407T>G		intron_variant	Intron 6 of 20	1		ENSP00000334703.3
COG5	ENST00000393603.7	c.538+28407T>G		intron_variant	Intron 6 of 20	1		ENSP00000377228.3
COG5	ENST00000475638.6	n.295+28407T>G		intron_variant	Intron 4 of 5	3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19105 AN: 152082 Hom.: 1505 Cov.: 32

Gnomad AFR AF: 0.0335

Gnomad AMI AF: 0.224

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.125 AC: 19099 AN: 152200 Hom.: 1503 Cov.: 32 AF XY: 0.124 AC XY: 9250 AN XY: 74404

African (AFR) AF: 0.0334 AC: 1386 AN: 41544

American (AMR) AF: 0.132 AC: 2020 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.157 AC: 545 AN: 3468

East Asian (EAS) AF: 0.135 AC: 699 AN: 5178

South Asian (SAS) AF: 0.135 AC: 651 AN: 4828

European-Finnish (FIN) AF: 0.154 AC: 1629 AN: 10594

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11664 AN: 68000

Other (OTH) AF: 0.126 AC: 267 AN: 2112

Alfa AF: 0.0449 Hom.: 57

Bravo AF: 0.123

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.5
DANN	Benign	0.65
PhyloP100		-0.099
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: rs12535761; hg19: chr7-107139275;