rs144989249

Variant names:

• chr17-73206698-T-G
• rs144989249
• NM_018714.3:c.2620-10T>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_018714.3(COG1):​c.2620-10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000949 in 1,600,342 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (6 hom., cov: 27)
  • Exomes 𝑓: 0.00056 (6 hom.)
• Consequence: COG1 NM_018714.3 intron
• Scores: Splicing: ADA: 0.007375
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0130
• Publications: 0 publications found

Genes affected

COG1 (HGNC:6545): (component of oligomeric golgi complex 1) 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. It is thought that this protein is required for steps in the normal medial and trans Golgi-associated processing of glycoconjugates and plays a role in the organization of the Golgi-localized complex. [provided by RefSeq, Jul 2008]

COG1 Gene-Disease associations (from GenCC):

• COG1-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P, PanelApp Australia, ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 17-73206698-T-G is Benign according to our data. Variant chr17-73206698-T-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 324974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00473 (714/151092) while in subpopulation AFR AF = 0.016 (658/41014). AF 95% confidence interval is 0.015. There are 6 homozygotes in GnomAd4. There are 309 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018714.3. 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
	COG1	NM_018714.3	MANE Select	c.2620-10T>G		intron	N/A	NP_061184.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG1	ENST00000299886.9	TSL:1 MANE Select	c.2620-10T>G		intron	N/A	ENSP00000299886.4
	COG1	ENST00000438720.7	TSL:1	c.2617-10T>G		intron	N/A	ENSP00000400111.3
	COG1	ENST00000923183.1		c.2614-10T>G		intron	N/A	ENSP00000593242.1

Frequencies

GnomAD3 genomes AF: 0.00472 AC: 712 AN: 150974 Hom.: 6 Cov.: 27

Gnomad AFR AF: 0.0160

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00191

Gnomad ASJ AF: 0.00318

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.00482

GnomAD2 exomes AF: 0.00136 AC: 341 AN: 251300 AF XY: 0.000935

Gnomad AFR exome AF: 0.0152

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00288

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000555 AC: 805 AN: 1449250 Hom.: 6 Cov.: 29 AF XY: 0.000475 AC XY: 343 AN XY: 721988

African (AFR) AF: 0.0148 AC: 491 AN: 33198

American (AMR) AF: 0.00148 AC: 66 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00238 AC: 62 AN: 26048

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.0000465 AC: 4 AN: 85976

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00122 AC: 7 AN: 5736

European-Non Finnish (NFE) AF: 0.0000800 AC: 88 AN: 1100622

Other (OTH) AF: 0.00145 AC: 87 AN: 59986

GnomAD4 genome AF: 0.00473 AC: 714 AN: 151092 Hom.: 6 Cov.: 27 AF XY: 0.00419 AC XY: 309 AN XY: 73778

African (AFR) AF: 0.0160 AC: 658 AN: 41014

American (AMR) AF: 0.00191 AC: 29 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.00318 AC: 11 AN: 3458

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4718

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10510

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0000738 AC: 5 AN: 67790

Other (OTH) AF: 0.00477 AC: 10 AN: 2096

Alfa AF: 0.00448 Hom.: 1

Bravo AF: 0.00532

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	COG1 congenital disorder of glycosylation (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.63
DANN	Benign	0.70
PhyloP100		-0.013
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0074
dbscSNV1_RF	Benign	0.30
SpliceAI score (max)		0.010		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: rs144989249; hg19: chr17-71202837;