rs1548524

Variant names:

• chr7-107304118-A-C
• rs1548524
• NM_006348.5:c.1109-5772T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-107304118-A-C
• chr7-107304118-A-T

Variant summary

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

The NM_006348.5(COG5):​c.1109-5772T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.166 in 152,180 control chromosomes in the GnomAD database, including 2,417 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 0.17 (2417 hom., cov: 32)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 12 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=-0.99).
• 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.1109-5772T>G		intron_variant	Intron 11 of 21	ENST00000297135.9	NP_006339.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG5	ENST00000297135.9	c.1109-5772T>G		intron_variant	Intron 11 of 21	1	NM_006348.5	ENSP00000297135.4
COG5	ENST00000347053.8	c.1109-5772T>G		intron_variant	Intron 11 of 20	1		ENSP00000334703.3
COG5	ENST00000393603.7	c.1109-5772T>G		intron_variant	Intron 11 of 20	1		ENSP00000377228.3

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25310 AN: 152062 Hom.: 2420 Cov.: 32

Gnomad AFR AF: 0.0776

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.166 AC: 25312 AN: 152180 Hom.: 2417 Cov.: 32 AF XY: 0.164 AC XY: 12210 AN XY: 74400

African (AFR) AF: 0.0777 AC: 3228 AN: 41548

American (AMR) AF: 0.171 AC: 2616 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3470

East Asian (EAS) AF: 0.139 AC: 718 AN: 5180

South Asian (SAS) AF: 0.176 AC: 850 AN: 4818

European-Finnish (FIN) AF: 0.169 AC: 1792 AN: 10588

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

European-Non Finnish (NFE) AF: 0.216 AC: 14699 AN: 67974

Other (OTH) AF: 0.172 AC: 363 AN: 2114

Alfa AF: 0.200 Hom.: 5499

Bravo AF: 0.165

Asia WGS AF: 0.177 AC: 615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	6.3
DANN	Benign	0.74
PhyloP100		-0.35
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: rs1548524; hg19: chr7-106944563;