dbSNP rs924812: COLQ:c.529-23A>G (chr3-15474974-T-C) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005677.4(COLQ):c.529-23A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 1,610,502 control chromosomes in the GnomAD database, including 125,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.37 ( 10770 hom., cov: 32)

Exomes 𝑓: 0.39 ( 114854 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.957

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

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 3-15474974-T-C is Benign according to our data. Variant chr3-15474974-T-C is described in ClinVar as Benign. ClinVar VariationId is 259860.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.

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.529-23A>G	intron	N/A	NP_005668.2
COLQ	NM_080538.2		c.499-23A>G	intron	N/A	NP_536799.1	Q9Y215-2
COLQ	NM_080539.4		c.427-23A>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.529-23A>G	intron	N/A	ENSP00000373298.3	Q9Y215-1
COLQ	ENST00000603808.5	TSL:1	c.529-23A>G	intron	N/A	ENSP00000474271.1	A0A0C4DGS2
COLQ	ENST00000874202.1		c.529-23A>G	intron	N/A	ENSP00000544261.1

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56795

AN:

151988

Hom.:

10769

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.370

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:

0.383

AC:

96300

AN:

251278

AF XY:

0.385

show subpopulations

Gnomad AFR exome

AF:

0.330

Gnomad AMR exome

AF:

0.331

Gnomad ASJ exome

AF:

0.466

Gnomad EAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.344

Gnomad NFE exome

AF:

0.391

Gnomad OTH exome

AF:

0.374

GnomAD4 exome

AF:

0.394

AC:

575120

AN:

1458396

Hom.:

114854

Cov.:

AF XY:

0.394

AC XY:

285994

AN XY:

725656

show subpopulations

African (AFR)

AF:

0.322

AC:

10767

AN:

33404

American (AMR)

AF:

0.336

AC:

15024

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

12105

AN:

26106

East Asian (EAS)

AF:

0.482

AC:

19122

AN:

39688

South Asian (SAS)

AF:

0.390

AC:

33605

AN:

86184

European-Finnish (FIN)

AF:

0.341

AC:

18207

AN:

53332

Middle Eastern (MID)

AF:

0.394

AC:

2270

AN:

5758

European-Non Finnish (NFE)

AF:

0.396

AC:

439685

AN:

1108920

Other (OTH)

AF:

0.404

AC:

24335

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

16229

32459

48688

64918

81147

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13814

27628

41442

55256

69070

<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:

56820

AN:

152106

Hom.:

10770

Cov.:

AF XY:

0.374

AC XY:

27822

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.328

AC:

13601

AN:

41500

American (AMR)

AF:

0.369

AC:

5645

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.471

AC:

1634

AN:

3470

East Asian (EAS)

AF:

0.489

AC:

2529

AN:

5168

South Asian (SAS)

AF:

0.381

AC:

1841

AN:

4826

European-Finnish (FIN)

AF:

0.352

AC:

3726

AN:

10580

Middle Eastern (MID)

AF:

0.364

AC:

107

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26408

AN:

67952

Other (OTH)

AF:

0.403

AC:

852

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1853

3707

5560

7414

9267

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:

0.387

Hom.:

2581

Bravo

AF:

0.374

Asia WGS

AF:

0.368

AC:

1279

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

-0.49

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

0.96

BranchPoint Hunter

3.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.25

Position offset: 5

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over