Genetic Variant NM_005677.4:c.394-27C>G (chr3-15477224-G-C) – ACMG Classification: Benign (-20 pts)

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.394-27C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 1,585,112 control chromosomes in the GnomAD database, including 127,762 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.39 ( 11482 hom., cov: 31)

Exomes 𝑓: 0.40 ( 116280 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.44

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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

COLQ links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_005677.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.82).

BP6

Variant 3-15477224-G-C is Benign according to our data. Variant chr3-15477224-G-C is described in ClinVar as Benign. ClinVar VariationId is 259857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COLQ	NM_005677.4	MANE Select	c.394-27C>G	intron	N/A	NP_005668.2
COLQ	NM_080538.2		c.364-27C>G	intron	N/A	NP_536799.1	Q9Y215-2
COLQ	NM_080539.4		c.292-27C>G	intron	N/A	NP_536800.2	Q9Y215-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
COLQ	ENST00000383788.10	TSL:1 MANE Select	c.394-27C>G	intron	N/A	ENSP00000373298.3	Q9Y215-1
COLQ	ENST00000603808.5	TSL:1	c.394-27C>G	intron	N/A	ENSP00000474271.1	A0A0C4DGS2
COLQ	ENST00000874202.1		c.394-27C>G	intron	N/A	ENSP00000544261.1

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58651

AN:

151868

Hom.:

11471

Cov.:

show subpopulations

Gnomad AFR

AF:

0.355

Gnomad AMI

AF:

0.530

Gnomad AMR

AF:

0.380

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.519

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.353

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.394

Gnomad OTH

AF:

0.417

GnomAD2 exomes

AF:

0.397

AC:

82162

AN:

207136

AF XY:

0.399

show subpopulations

Gnomad AFR exome

AF:

0.359

Gnomad AMR exome

AF:

0.343

Gnomad ASJ exome

AF:

0.470

Gnomad EAS exome

AF:

0.514

Gnomad FIN exome

AF:

0.349

Gnomad NFE exome

AF:

0.403

Gnomad OTH exome

AF:

0.388

GnomAD4 exome

AF:

0.401

AC:

574757

AN:

1433126

Hom.:

116280

Cov.:

AF XY:

0.401

AC XY:

284708

AN XY:

710446

show subpopulations

African (AFR)

AF:

0.352

AC:

11665

AN:

33126

American (AMR)

AF:

0.345

AC:

14095

AN:

40820

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

11876

AN:

25422

East Asian (EAS)

AF:

0.502

AC:

19548

AN:

38916

South Asian (SAS)

AF:

0.393

AC:

32373

AN:

82302

European-Finnish (FIN)

AF:

0.343

AC:

17702

AN:

51618

Middle Eastern (MID)

AF:

0.411

AC:

2352

AN:

5722

European-Non Finnish (NFE)

AF:

0.402

AC:

440498

AN:

1095876

Other (OTH)

AF:

0.415

AC:

24648

AN:

59324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

17157

34314

51472

68629

85786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13896

27792

41688

55584

69480

<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:

0.386

AC:

58701

AN:

151986

Hom.:

11482

Cov.:

AF XY:

0.386

AC XY:

28709

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.355

AC:

14724

AN:

41446

American (AMR)

AF:

0.380

AC:

5794

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

1644

AN:

3466

East Asian (EAS)

AF:

0.518

AC:

2667

AN:

5146

South Asian (SAS)

AF:

0.386

AC:

1860

AN:

4816

European-Finnish (FIN)

AF:

0.353

AC:

3736

AN:

10576

Middle Eastern (MID)

AF:

0.381

AC:

112

AN:

294

European-Non Finnish (NFE)

AF:

0.394

AC:

26798

AN:

67956

Other (OTH)

AF:

0.419

AC:

884

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1826

3653

5479

7306

9132

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

564

1128

1692

2256

2820

<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:

0.397

Hom.:

2222

Bravo

AF:

0.388

Asia WGS

AF:

0.400

AC:

1391

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital myasthenic syndrome 5 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.9

(source)

DANN

Benign

0.58

PhyloP100

1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over