Variant 16-70510030-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015386.3(COG4):c.739-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0234 in 1,609,788 control chromosomes in the GnomAD database, including 6,841 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 3652 hom., cov: 32)

Exomes 𝑓: 0.013 ( 3189 hom. )

Consequence

COG4
NM_015386.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002747

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.393

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 16-70510030-G-C is Benign according to our data. Variant chr16-70510030-G-C is described in ClinVar as [Benign]. Clinvar id is 320377.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.408 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COG4	NM_015386.3 linkuse as main transcript	c.739-9C>G	splice_polypyrimidine_tract_variant, intron_variant	ENST00000323786.10
COG4	NM_001195139.2 linkuse as main transcript	c.727-9C>G	splice_polypyrimidine_tract_variant, intron_variant
COG4	NM_001365426.1 linkuse as main transcript	c.313-9C>G	splice_polypyrimidine_tract_variant, intron_variant
COG4	NR_158212.1 linkuse as main transcript	n.750-9C>G	splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COG4	ENST00000323786.10 linkuse as main transcript	c.739-9C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015386.3	P1

Frequencies

GnomAD3 genomes

AF:

0.120

AC:

18253

AN:

152042

Hom.:

3648

Cov.:

show subpopulations

Gnomad AFR

AF:

0.414

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0450

Gnomad ASJ

AF:

0.0251

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00266

Gnomad OTH

AF:

0.0798

GnomAD3 exomes

AF:

0.0326

AC:

8169

AN:

250946

Hom.:

1434

AF XY:

0.0242

AC XY:

3278

AN XY:

135722

show subpopulations

Gnomad AFR exome

AF:

0.417

Gnomad AMR exome

AF:

0.0210

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00215

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0133

AC:

19356

AN:

1457628

Hom.:

3189

Cov.:

AF XY:

0.0117

AC XY:

8458

AN XY:

725438

show subpopulations

Gnomad4 AFR exome

AF:

0.420

Gnomad4 AMR exome

AF:

0.0230

Gnomad4 ASJ exome

AF:

0.0314

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000778

Gnomad4 FIN exome

AF:

0.0000938

Gnomad4 NFE exome

AF:

0.00134

Gnomad4 OTH exome

AF:

0.0290

GnomAD4 genome

AF:

0.120

AC:

18287

AN:

152160

Hom.:

3652

Cov.:

AF XY:

0.117

AC XY:

8695

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.413

Gnomad4 AMR

AF:

0.0449

Gnomad4 ASJ

AF:

0.0251

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00266

Gnomad4 OTH

AF:

0.0789

Alfa

AF:

0.0116

Hom.:

Bravo

AF:

0.135

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 22, 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-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

May 08, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

COG4-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.6

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.062

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

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