rs3762171

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015386.3(COG4):c.646C>T(p.Leu216Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 1,613,736 control chromosomes in the GnomAD database, including 154,948 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 12317 hom., cov: 32)

Exomes 𝑓: 0.44 ( 142631 hom. )

Consequence

COG4
NM_015386.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 3.38

Variant links:

Genes affected

COG4 (HGNC:18620): (component of oligomeric golgi complex 4) The protein encoded by this gene is a component of an oligomeric protein complex involved in the structure and function of the Golgi apparatus. Defects in this gene may be a cause of congenital disorder of glycosylation type IIj. Two transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Aug 2010]

COG4 links:

COG4 (HGNC:):

COG4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 16-70512331-G-A is Benign according to our data. Variant chr16-70512331-G-A is described in ClinVar as [Benign]. Clinvar id is 95699.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-70512331-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=3.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.63 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COG4	NM_015386.3 linkuse as main transcript	c.646C>T	p.Leu216Leu	synonymous_variant	5/19	ENST00000323786.10	NP_056201.2	Q9H9E3J3KNI1Q8N8L9
COG4	NM_001195139.2 linkuse as main transcript	c.634C>T	p.Leu212Leu	synonymous_variant	5/18		NP_001182068.2	Q9H9E3A0A0A0MS45Q8N8L9
COG4	NM_001365426.1 linkuse as main transcript	c.220C>T	p.Leu74Leu	synonymous_variant	6/20		NP_001352355.1
COG4	NR_158212.1 linkuse as main transcript	n.657C>T		non_coding_transcript_exon_variant	5/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COG4	ENST00000323786.10 linkuse as main transcript	c.646C>T	p.Leu216Leu	synonymous_variant	5/19	1	NM_015386.3	ENSP00000315775.5		J3KNI1

Frequencies

GnomAD3 genomes

AF:

0.394

AC:

59812

AN:

151834

Hom.:

12310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.286

Gnomad AMI

AF:

0.363

Gnomad AMR

AF:

0.448

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.575

Gnomad SAS

AF:

0.648

Gnomad FIN

AF:

0.351

Gnomad MID

AF:

0.503

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.423

GnomAD3 exomes

AF:

0.453

AC:

113729

AN:

250938

Hom.:

27083

AF XY:

0.464

AC XY:

62994

AN XY:

135650

show subpopulations

Gnomad AFR exome

AF:

0.284

Gnomad AMR exome

AF:

0.460

Gnomad ASJ exome

AF:

0.441

Gnomad EAS exome

AF:

0.586

Gnomad SAS exome

AF:

0.646

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.423

Gnomad OTH exome

AF:

0.457

GnomAD4 exome

AF:

0.436

AC:

637618

AN:

1461784

Hom.:

142631

Cov.:

AF XY:

0.443

AC XY:

321904

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.457

Gnomad4 ASJ exome

AF:

0.430

Gnomad4 EAS exome

AF:

0.548

Gnomad4 SAS exome

AF:

0.642

Gnomad4 FIN exome

AF:

0.345

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.450

GnomAD4 genome

AF:

0.394

AC:

59847

AN:

151952

Hom.:

12317

Cov.:

AF XY:

0.398

AC XY:

29583

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.286

Gnomad4 AMR

AF:

0.448

Gnomad4 ASJ

AF:

0.427

Gnomad4 EAS

AF:

0.575

Gnomad4 SAS

AF:

0.649

Gnomad4 FIN

AF:

0.351

Gnomad4 NFE

AF:

0.420

Gnomad4 OTH

AF:

0.423

Alfa

AF:

0.421

Hom.:

26892

Bravo

AF:

0.394

Asia WGS

AF:

0.623

AC:

2166

AN:

3478

EpiCase

AF:

0.433

EpiControl

AF:

0.438

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 11, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

COG4-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 22, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Microcephalic osteodysplastic dysplasia, Saul-Wilson type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 22, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Benign

0.74

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over