Genetic Variant COG7:c.170-12_170-9delTTTT (chr16-23445969-TAAAA-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6

The NM_153603.4(COG7):c.170-12_170-9delTTTT variant causes a intron change. The variant allele was found at a frequency of 0.000179 in 1,360,076 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00018 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

COG7
NM_153603.4 intron

Scores

Not classified

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.00

Publications

2 publications found

Variant links:

Genes affected

COG7 (HGNC:18622): (component of oligomeric golgi complex 7) The protein encoded by this gene resides in the golgi, and constitutes one of the 8 subunits of the conserved oligomeric Golgi (COG) complex, which is required for normal golgi morphology and localization. Mutations in this gene are associated with the congenital disorder of glycosylation type IIe.[provided by RefSeq, May 2010]

COG7 Gene-Disease associations (from GenCC):

COG7-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, G2P, Orphanet

COG7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP6

Variant 16-23445969-TAAAA-T is Benign according to our data. Variant chr16-23445969-TAAAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3040291.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COG7	NM_153603.4 link	c.170-12_170-9delTTTT		intron_variant	Intron 1 of 16	ENST00000307149.10	NP_705831.1	P83436A0A0S2Z652
COG7	XM_017023870.2 link	c.-26-12_-26-9delTTTT		intron_variant	Intron 1 of 16		XP_016879359.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COG7	ENST00000307149.10 link	c.170-12_170-9delTTTT		intron_variant	Intron 1 of 16	1	NM_153603.4	ENSP00000305442.5		P83436

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

129250

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000446

AC:

AN:

152462

AF XY:

0.000470

show subpopulations

Gnomad AFR exome

AF:

0.0000986

Gnomad AMR exome

AF:

0.000137

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000489

Gnomad FIN exome

AF:

0.000521

Gnomad NFE exome

AF:

0.000607

Gnomad OTH exome

AF:

0.000521

GnomAD4 exome

AF:

0.000179

AC:

244

AN:

1360076

Hom.:

AF XY:

0.000186

AC XY:

126

AN XY:

677608

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000267

AC:

AN:

29928

American (AMR)

AF:

0.000416

AC:

AN:

38476

Ashkenazi Jewish (ASJ)

AF:

0.000163

AC:

AN:

24602

East Asian (EAS)

AF:

0.000212

AC:

AN:

37650

South Asian (SAS)

AF:

0.000151

AC:

AN:

79222

European-Finnish (FIN)

AF:

0.000362

AC:

AN:

41414

Middle Eastern (MID)

AF:

0.000197

AC:

AN:

5080

European-Non Finnish (NFE)

AF:

0.000162

AC:

170

AN:

1047192

Other (OTH)

AF:

0.000177

AC:

AN:

56512

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.245

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

129250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

62170

African (AFR)

AF:

0.00

AC:

AN:

34996

American (AMR)

AF:

0.00

AC:

AN:

12620

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3108

East Asian (EAS)

AF:

0.00

AC:

AN:

4592

South Asian (SAS)

AF:

0.00

AC:

AN:

4122

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

59864

Other (OTH)

AF:

0.00

AC:

AN:

1738

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

COG7-related disorder

Benign:1

Jan 03, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

4.0

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over