rs200529572

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005677.4(COLQ):c.107-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,610,092 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 5 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.865

Publications

0 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=-0.64).

BP6

Variant 3-15489656-C-T is Benign according to our data. Variant chr3-15489656-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0014 (213/152340) while in subpopulation NFE AF = 0.00193 (131/68032). AF 95% confidence interval is 0.00166. There are 0 homozygotes in GnomAd4. There are 113 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COLQ	NM_005677.4 link	c.107-19G>A	intron_variant	Intron 1 of 16	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2 link	c.77-19G>A	intron_variant	Intron 1 of 16		NP_536799.1
COLQ	NM_080539.4 link	c.107-19G>A	intron_variant	Intron 1 of 15		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10 link	c.107-19G>A		intron_variant	Intron 1 of 16	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5 link	c.107-19G>A		intron_variant	Intron 1 of 16	1		ENSP00000474271.1

Frequencies

GnomAD3 genomes

AF:

0.00140

AC:

213

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.0285

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00169

AC:

417

AN:

246474

AF XY:

0.00185

show subpopulations

Gnomad AFR exome

AF:

0.000692

Gnomad AMR exome

AF:

0.000614

Gnomad ASJ exome

AF:

0.00111

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000616

Gnomad NFE exome

AF:

0.00252

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00220

AC:

3213

AN:

1457752

Hom.:

Cov.:

AF XY:

0.00217

AC XY:

1576

AN XY:

725232

show subpopulations

African (AFR)

AF:

0.000210

AC:

AN:

33402

American (AMR)

AF:

0.000562

AC:

AN:

44512

Ashkenazi Jewish (ASJ)

AF:

0.00119

AC:

AN:

26064

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39632

South Asian (SAS)

AF:

0.00249

AC:

214

AN:

85862

European-Finnish (FIN)

AF:

0.000863

AC:

AN:

53290

Middle Eastern (MID)

AF:

0.000718

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.00251

AC:

2781

AN:

1109212

Other (OTH)

AF:

0.00171

AC:

103

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

164

327

491

654

818

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.00140

AC:

213

AN:

152340

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

113

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.000601

AC:

AN:

41576

American (AMR)

AF:

0.00111

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00115

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00125

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00150

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 29, 2016

GeneDx

Significance:Likely 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. -

Congenital myasthenic syndrome 5

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

6.1

(source)

DANN

Benign

0.87

PhyloP100

-0.86

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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