3-15475403-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005677.4(COLQ):c.528+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,577,442 control chromosomes in the GnomAD database, including 123,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10763 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112337 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.209

Publications

9 publications found

Variant links:

Genes affected

COLQ (HGNC:2226): (collagen like tail subunit of asymmetric acetylcholinesterase) This gene encodes the subunit of a collagen-like molecule associated with acetylcholinesterase in skeletal muscle. Each molecule is composed of three identical subunits. Each subunit contains a proline-rich attachment domain (PRAD) that binds an acetylcholinesterase tetramer to anchor the catalytic subunit of the enzyme to the basal lamina. Mutations in this gene are associated with endplate acetylcholinesterase deficiency. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

COLQ Gene-Disease associations (from GenCC):

congenital myasthenic syndrome 5
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia

COLQ links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-15475403-T-C is Benign according to our data. Variant chr3-15475403-T-C is described in ClinVar as Benign. ClinVar VariationId is 259859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4 link	c.528+22A>G	intron_variant	Intron 7 of 16	ENST00000383788.10	NP_005668.2	Q9Y215-1
COLQ	NM_080538.2 link	c.498+22A>G	intron_variant	Intron 7 of 16		NP_536799.1	Q9Y215-2
COLQ	NM_080539.4 link	c.426+22A>G	intron_variant	Intron 6 of 15		NP_536800.2	Q9Y215-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10 link	c.528+22A>G		intron_variant	Intron 7 of 16	1	NM_005677.4	ENSP00000373298.3		Q9Y215-1
COLQ	ENST00000603808.5 link	c.528+22A>G		intron_variant	Intron 7 of 16	1		ENSP00000474271.1		A0A0C4DGS2

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56760

AN:

151914

Hom.:

10762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.471

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.402

GnomAD2 exomes

AF:

0.385

AC:

77877

AN:

202484

AF XY:

0.386

show subpopulations

Gnomad AFR exome

AF:

0.329

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.479

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.395

AC:

562713

AN:

1425410

Hom.:

112337

Cov.:

AF XY:

0.395

AC XY:

278474

AN XY:

705812

show subpopulations

African (AFR)

AF:

0.322

AC:

10587

AN:

32868

American (AMR)

AF:

0.338

AC:

13712

AN:

40540

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

11793

AN:

25444

East Asian (EAS)

AF:

0.482

AC:

18609

AN:

38644

South Asian (SAS)

AF:

0.389

AC:

31835

AN:

81762

European-Finnish (FIN)

AF:

0.342

AC:

17507

AN:

51186

Middle Eastern (MID)

AF:

0.391

AC:

1997

AN:

5102

European-Non Finnish (NFE)

AF:

0.397

AC:

432831

AN:

1090956

Other (OTH)

AF:

0.405

AC:

23842

AN:

58908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

15212

30423

45635

60846

76058

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13724

27448

41172

54896

68620

<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

AF:

0.374

AC:

56785

AN:

152032

Hom.:

10763

Cov.:

AF XY:

0.374

AC XY:

27775

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.328

AC:

13598

AN:

41496

American (AMR)

AF:

0.369

AC:

5631

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1635

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2519

AN:

5152

South Asian (SAS)

AF:

0.382

AC:

1840

AN:

4818

European-Finnish (FIN)

AF:

0.352

AC:

3718

AN:

10548

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26412

AN:

67970

Other (OTH)

AF:

0.402

AC:

848

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1797

3594

5392

7189

8986

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.388

Hom.:

15477

Bravo

AF:

0.374

Asia WGS

AF:

0.369

AC:

1281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome 5

Benign:1

Jul 30, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.5

(source)

DANN

Benign

0.46

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over