NM_005677.4:c.106+6T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1

The NM_005677.4(COLQ):​c.106+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0016 ( 1 hom. )

Consequence

COLQ
NM_005677.4 splice_region, intron

Scores

2
Splicing: ADA: 0.0001462
2

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:2

Conservation

PhyloP100: -1.01

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

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 3-15521514-A-G is Benign according to our data. Variant chr3-15521514-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 287047.We mark this variant Likely_benign, oryginal submission is: [Conflicting_classifications_of_pathogenicity].
BS1
Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00116 (177/152284) while in subpopulation NFE AF = 0.0021 (143/68030). AF 95% confidence interval is 0.00182. There are 0 homozygotes in GnomAd4. There are 75 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
COLQNM_005677.4 linkc.106+6T>C splice_region_variant, intron_variant Intron 1 of 16 ENST00000383788.10 NP_005668.2 Q9Y215-1
COLQNM_080539.4 linkc.106+6T>C splice_region_variant, intron_variant Intron 1 of 15 NP_536800.2 Q9Y215-3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
COLQENST00000383788.10 linkc.106+6T>C splice_region_variant, intron_variant Intron 1 of 16 1 NM_005677.4 ENSP00000373298.3 Q9Y215-1
COLQENST00000603808.5 linkc.106+6T>C splice_region_variant, intron_variant Intron 1 of 16 1 ENSP00000474271.1 A0A0C4DGS2

Frequencies

GnomAD3 genomes
AF:
0.00116
AC:
177
AN:
152166
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000917
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000621
Gnomad FIN
AF:
0.000942
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00210
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.00100
AC:
252
AN:
251418
AF XY:
0.00102
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000520
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000972
Gnomad NFE exome
AF:
0.00174
Gnomad OTH exome
AF:
0.00163
GnomAD4 exome
AF:
0.00164
AC:
2395
AN:
1461846
Hom.:
1
Cov.:
32
AF XY:
0.00161
AC XY:
1173
AN XY:
727224
show subpopulations
African (AFR)
AF:
0.000179
AC:
6
AN:
33480
American (AMR)
AF:
0.000671
AC:
30
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.000185
AC:
16
AN:
86258
European-Finnish (FIN)
AF:
0.000843
AC:
45
AN:
53382
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00199
AC:
2218
AN:
1112004
Other (OTH)
AF:
0.00132
AC:
80
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
120
241
361
482
602
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
84
168
252
336
420
<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:
0.00116
AC:
177
AN:
152284
Hom.:
0
Cov.:
32
AF XY:
0.00101
AC XY:
75
AN XY:
74466
show subpopulations
African (AFR)
AF:
0.000168
AC:
7
AN:
41558
American (AMR)
AF:
0.000916
AC:
14
AN:
15290
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5180
South Asian (SAS)
AF:
0.000622
AC:
3
AN:
4826
European-Finnish (FIN)
AF:
0.000942
AC:
10
AN:
10612
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.00210
AC:
143
AN:
68030
Other (OTH)
AF:
0.00
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.509
Heterozygous variant carriers
0
10
20
29
39
49
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
4
8
12
16
20
<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:
0.00143
Hom.:
1
Bravo
AF:
0.00117

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:2Benign:2
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 5 Uncertain:1Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Jan 19, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Uncertain:1
Apr 20, 2016
Eurofins Ntd Llc (ga)
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

COLQ-related disorder Benign:1
Apr 02, 2021
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
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.077
DANN
Benign
0.34
PhyloP100
-1.0
PromoterAI
-0.039
Neutral
Mutation Taster
=97/3
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00015
dbscSNV1_RF
Benign
0.070
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

Other links and lift over

dbSNP: rs201376373; hg19: chr3-15563021; API