rs35581984

Variant names:

• chr7-107248422-G-A
• rs35581984
• NM_006348.5:c.1827C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_006348.5(COG5):​c.1827C>T​(p.Ile609Ile) variant causes a synonymous change. The variant allele was found at a frequency of 0.0377 in 1,610,482 control chromosomes in the GnomAD database, including 1,325 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (128 hom., cov: 31)
  • Exomes 𝑓: 0.038 (1197 hom.)
• Consequence: COG5 NM_006348.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.61
• Publications: 4 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: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BP6: Variant 7-107248422-G-A is Benign according to our data. Variant chr7-107248422-G-A is described in ClinVar as Benign. ClinVar VariationId is 358456.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.032 (4846/151620) while in subpopulation NFE AF = 0.0465 (3160/67940). AF 95% confidence interval is 0.0452. There are 128 homozygotes in GnomAd4. There are 2321 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 128 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006348.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	NM_006348.5	MANE Select	c.1827C>T	p.Ile609Ile	synonymous	Exon 17 of 22	NP_006339.4
	COG5	NM_181733.4		c.1764C>T	p.Ile588Ile	synonymous	Exon 16 of 21	NP_859422.3	A0AAA9X096
	COG5	NM_001161520.2		c.1827C>T	p.Ile609Ile	synonymous	Exon 17 of 21	NP_001154992.2	A0AAA9X2X8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG5	ENST00000297135.9	TSL:1 MANE Select	c.1827C>T	p.Ile609Ile	synonymous	Exon 17 of 22	ENSP00000297135.4	Q9UP83-4
	COG5	ENST00000347053.8	TSL:1	c.1764C>T	p.Ile588Ile	synonymous	Exon 16 of 21	ENSP00000334703.3	A0AAA9X096
	COG5	ENST00000393603.7	TSL:1	c.1827C>T	p.Ile609Ile	synonymous	Exon 17 of 21	ENSP00000377228.3	A0AAA9X2X8

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4846 AN: 151504 Hom.: 128 Cov.: 31

Gnomad AFR AF: 0.00970

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00668

Gnomad FIN AF: 0.0454

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0465

Gnomad OTH AF: 0.0380

GnomAD2 exomes AF: 0.0322 AC: 8096 AN: 251292 AF XY: 0.0320

Gnomad AFR exome AF: 0.00849

Gnomad AMR exome AF: 0.0225

Gnomad ASJ exome AF: 0.0561

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0432

Gnomad NFE exome AF: 0.0461

Gnomad OTH exome AF: 0.0364

GnomAD4 exome AF: 0.0383 AC: 55895 AN: 1458862 Hom.: 1197 Cov.: 30 AF XY: 0.0376 AC XY: 27289 AN XY: 725866

African (AFR) AF: 0.00751 AC: 251 AN: 33440

American (AMR) AF: 0.0235 AC: 1052 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.0571 AC: 1491 AN: 26114

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39670

South Asian (SAS) AF: 0.00718 AC: 619 AN: 86218

European-Finnish (FIN) AF: 0.0425 AC: 2261 AN: 53240

Middle Eastern (MID) AF: 0.0153 AC: 88 AN: 5760

European-Non Finnish (NFE) AF: 0.0433 AC: 48045 AN: 1109406

Other (OTH) AF: 0.0346 AC: 2086 AN: 60304

GnomAD4 genome AF: 0.0320 AC: 4846 AN: 151620 Hom.: 128 Cov.: 31 AF XY: 0.0313 AC XY: 2321 AN XY: 74080

African (AFR) AF: 0.00968 AC: 400 AN: 41342

American (AMR) AF: 0.0317 AC: 482 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.0577 AC: 200 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5140

South Asian (SAS) AF: 0.00690 AC: 33 AN: 4782

European-Finnish (FIN) AF: 0.0454 AC: 473 AN: 10428

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0465 AC: 3160 AN: 67940

Other (OTH) AF: 0.0376 AC: 79 AN: 2102

Alfa AF: 0.0424 Hom.: 292

Bravo AF: 0.0297

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.0415

EpiControl AF: 0.0443

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	COG5-congenital disorder of glycosylation (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
CADD	Benign	8.4
DANN	Benign	0.73
PhyloP100		3.6
Mutation Taster		=97/3	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: rs35581984; hg19: chr7-106888867; COSMIC: COSV51751114;