dbSNP rs12633820: COLQ:c.1299-782C>T (chr3-15452495-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005677.4(COLQ):c.1299-782C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 152,058 control chromosomes in the GnomAD database, including 9,793 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.35 ( 9793 hom., cov: 32)

Consequence

COLQ
NM_005677.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.452

Publications

2 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:

ENSG00000293553 (HGNC:):

ENSG00000293553 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
COLQ	NM_005677.4 link	c.1299-782C>T	intron_variant	Intron 16 of 16	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2 link	c.1269-782C>T	intron_variant	Intron 16 of 16		NP_536799.1
COLQ	NM_080539.4 link	c.1197-782C>T	intron_variant	Intron 15 of 15		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
COLQ	ENST00000383788.10 link	c.1299-782C>T	intron_variant	Intron 16 of 16	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5 link	c.1302-782C>T	intron_variant	Intron 16 of 16	1		ENSP00000474271.1
ENSG00000293553	ENST00000629729.3 link	n.*23-782C>T	intron_variant	Intron 2 of 5	5		ENSP00000518887.1

Frequencies

GnomAD3 genomes

AF:

0.354

AC:

53791

AN:

151940

Hom.:

9796

Cov.:

show subpopulations

Gnomad AFR

AF:

0.262

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.362

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.490

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.389

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.354

AC:

53806

AN:

152058

Hom.:

9793

Cov.:

AF XY:

0.354

AC XY:

26302

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.262

AC:

10878

AN:

41488

American (AMR)

AF:

0.362

AC:

5526

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.467

AC:

1619

AN:

3466

East Asian (EAS)

AF:

0.490

AC:

2538

AN:

5182

South Asian (SAS)

AF:

0.376

AC:

1809

AN:

4806

European-Finnish (FIN)

AF:

0.336

AC:

3545

AN:

10566

Middle Eastern (MID)

AF:

0.374

AC:

110

AN:

294

European-Non Finnish (NFE)

AF:

0.390

AC:

26480

AN:

67954

Other (OTH)

AF:

0.390

AC:

822

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1793

3585

5378

7170

8963

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

534

1068

1602

2136

2670

<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:

0.368

Hom.:

4550

Bravo

AF:

0.353

Asia WGS

AF:

0.367

AC:

1273

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.6

(source)

DANN

Benign

0.81

PhyloP100

-0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over