17-73200670-A-G

Variant names:

• chr17-73200670-A-G
• rs1026128
• NM_018714.3:c.1175A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_018714.3(COG1):​c.1175A>G​(p.Asn392Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.528 in 1,613,786 control chromosomes in the GnomAD database, including 226,214 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.51 (20179 hom., cov: 31)
  • Exomes 𝑓: 0.53 (206035 hom.)
• Consequence: COG1 NM_018714.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.27
• Publications: 54 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 (MetaRNN=5.2750896E-5).
• BP6: Variant 17-73200670-A-G is Benign according to our data. Variant chr17-73200670-A-G is described in ClinVar as Benign. ClinVar VariationId is 95911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

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.1175A>G	p.Asn392Ser	missense	Exon 6 of 14	NP_061184.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COG1	ENST00000299886.9	TSL:1 MANE Select	c.1175A>G	p.Asn392Ser	missense	Exon 6 of 14	ENSP00000299886.4
	COG1	ENST00000438720.7	TSL:1	c.1172A>G	p.Asn391Ser	missense	Exon 6 of 13	ENSP00000400111.3
	COG1	ENST00000923183.1		c.1169A>G	p.Asn390Ser	missense	Exon 6 of 14	ENSP00000593242.1

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78058 AN: 151884 Hom.: 20165 Cov.: 31

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.508

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.443

Gnomad EAS AF: 0.600

Gnomad SAS AF: 0.467

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.508

GnomAD2 exomes AF: 0.523 AC: 131411 AN: 251440 AF XY: 0.521

Gnomad AFR exome AF: 0.505

Gnomad AMR exome AF: 0.537

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.614

Gnomad FIN exome AF: 0.476

Gnomad NFE exome AF: 0.535

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.530 AC: 774170 AN: 1461784 Hom.: 206035 Cov.: 51 AF XY: 0.528 AC XY: 383816 AN XY: 727194

African (AFR) AF: 0.506 AC: 16949 AN: 33478

American (AMR) AF: 0.532 AC: 23776 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 11747 AN: 26132

East Asian (EAS) AF: 0.621 AC: 24672 AN: 39700

South Asian (SAS) AF: 0.477 AC: 41174 AN: 86256

European-Finnish (FIN) AF: 0.477 AC: 25504 AN: 53416

Middle Eastern (MID) AF: 0.563 AC: 3243 AN: 5764

European-Non Finnish (NFE) AF: 0.536 AC: 595641 AN: 1111924

Other (OTH) AF: 0.521 AC: 31464 AN: 60392

GnomAD4 genome AF: 0.514 AC: 78125 AN: 152002 Hom.: 20179 Cov.: 31 AF XY: 0.511 AC XY: 37951 AN XY: 74272

African (AFR) AF: 0.501 AC: 20774 AN: 41444

American (AMR) AF: 0.492 AC: 7512 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.443 AC: 1538 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3092 AN: 5156

South Asian (SAS) AF: 0.470 AC: 2264 AN: 4820

European-Finnish (FIN) AF: 0.481 AC: 5085 AN: 10566

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36168 AN: 67956

Other (OTH) AF: 0.512 AC: 1081 AN: 2112

Alfa AF: 0.527 Hom.: 96594

Bravo AF: 0.520

TwinsUK AF: 0.552 AC: 2048

ALSPAC AF: 0.530 AC: 2043

ESP6500AA AF: 0.517 AC: 2280

ESP6500EA AF: 0.540 AC: 4641

ExAC AF: 0.523 AC: 63485

Asia WGS AF: 0.527 AC: 1829 AN: 3478

EpiCase AF: 0.538

EpiControl AF: 0.539

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	COG1 congenital disorder of glycosylation (3)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.5
DANN	Benign	0.78
DEOGEN2	Benign	0.0018	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.000053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.75	N
PhyloP100		1.3
PrimateAI	Benign	0.23	T
PROVEAN	Benign	0.12	N
REVEL	Benign	0.041
Sift	Benign	0.64	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.013
MPC		0.080
ClinPred		0.0042	T
GERP RS		-2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.025
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1026128; hg19: chr17-71196809; COSMIC: COSV55428792; COSMIC: COSV55428792;