rs997311

Variant names:

• chr7-107312588-G-A
• rs997311
• NM_006348.5:c.1108+11852C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-107312588-G-A
• chr7-107312588-G-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.1108+11852C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,124 control chromosomes in the GnomAD database, including 2,320 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 (2320 hom., cov: 32)
• Consequence: COG5 NM_006348.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 8 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=-0.91).
• 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.1108+11852C>T		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.1108+11852C>T		intron_variant	Intron 11 of 21	1	NM_006348.5	ENSP00000297135.4
COG5	ENST00000347053.8	c.1108+11852C>T		intron_variant	Intron 11 of 20	1		ENSP00000334703.3
COG5	ENST00000393603.7	c.1108+11852C>T		intron_variant	Intron 11 of 20	1		ENSP00000377228.3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23783 AN: 152006 Hom.: 2323 Cov.: 32

Gnomad AFR AF: 0.0430

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.139

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.156 AC: 23777 AN: 152124 Hom.: 2320 Cov.: 32 AF XY: 0.154 AC XY: 11477 AN XY: 74366

African (AFR) AF: 0.0430 AC: 1785 AN: 41532

American (AMR) AF: 0.169 AC: 2575 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3468

East Asian (EAS) AF: 0.139 AC: 718 AN: 5166

South Asian (SAS) AF: 0.174 AC: 837 AN: 4818

European-Finnish (FIN) AF: 0.170 AC: 1792 AN: 10572

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

European-Non Finnish (NFE) AF: 0.216 AC: 14679 AN: 67976

Other (OTH) AF: 0.164 AC: 347 AN: 2112

Alfa AF: 0.203 Hom.: 1839

Bravo AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.70
PhyloP100		-0.17
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: rs997311; hg19: chr7-106953033;