NM_005677.4:c.600+40G>A

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.600+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,611,564 control chromosomes in the GnomAD database, including 157,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16738 hom., cov: 31)

Exomes 𝑓: 0.44 ( 140291 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Splicing: ADA: 0.00007013

Clinical Significance

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

Conservation

PhyloP100: -1.31

Publications

11 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=-0.9).

BP6

Variant 3-15474188-C-T is Benign according to our data. Variant chr3-15474188-C-T is described in ClinVar as Benign. ClinVar VariationId is 259862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4 link	c.600+40G>A	intron_variant	Intron 9 of 16	ENST00000383788.10	NP_005668.2	Q9Y215-1
COLQ	NM_080538.2 link	c.570+40G>A	intron_variant	Intron 9 of 16		NP_536799.1	Q9Y215-2
COLQ	NM_080539.4 link	c.498+40G>A	intron_variant	Intron 8 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.600+40G>A		intron_variant	Intron 9 of 16	1	NM_005677.4	ENSP00000373298.3		Q9Y215-1
COLQ	ENST00000603808.5 link	c.600+40G>A		intron_variant	Intron 9 of 16	1		ENSP00000474271.1		A0A0C4DGS2

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70467

AN:

151882

Hom.:

16717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.492

GnomAD2 exomes

AF:

0.428

AC:

107537

AN:

251300

AF XY:

0.427

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.489

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.427

Gnomad OTH exome

AF:

0.422

GnomAD4 exome

AF:

0.436

AC:

636338

AN:

1459564

Hom.:

140291

Cov.:

AF XY:

0.435

AC XY:

316272

AN XY:

726288

show subpopulations

African (AFR)

AF:

0.561

AC:

18737

AN:

33428

American (AMR)

AF:

0.372

AC:

16628

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

13207

AN:

26124

East Asian (EAS)

AF:

0.491

AC:

19501

AN:

39694

South Asian (SAS)

AF:

0.424

AC:

36591

AN:

86198

European-Finnish (FIN)

AF:

0.359

AC:

19147

AN:

53408

Middle Eastern (MID)

AF:

0.478

AC:

2750

AN:

5758

European-Non Finnish (NFE)

AF:

0.434

AC:

482122

AN:

1109920

Other (OTH)

AF:

0.458

AC:

27655

AN:

60328

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

18200

36399

54599

72798

90998

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14852

29704

44556

59408

74260

<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:

0.464

AC:

70540

AN:

152000

Hom.:

16738

Cov.:

AF XY:

0.461

AC XY:

34268

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.556

AC:

23047

AN:

41456

American (AMR)

AF:

0.433

AC:

6609

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

1792

AN:

3470

East Asian (EAS)

AF:

0.499

AC:

2577

AN:

5164

South Asian (SAS)

AF:

0.411

AC:

1978

AN:

4818

European-Finnish (FIN)

AF:

0.366

AC:

3860

AN:

10548

Middle Eastern (MID)

AF:

0.435

AC:

128

AN:

294

European-Non Finnish (NFE)

AF:

0.427

AC:

29018

AN:

67960

Other (OTH)

AF:

0.493

AC:

1040

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1941

3882

5824

7765

9706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<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:

0.457

Hom.:

10916

Bravo

AF:

0.474

Asia WGS

AF:

0.432

AC:

1499

AN:

3478

EpiCase

AF:

0.442

EpiControl

AF:

0.450

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

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. -

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

-0.90

CADD

Benign

0.12

(source)

DANN

Benign

0.46

PhyloP100

-1.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000070

dbscSNV1_RF

Benign

0.0020

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