3-15474974-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-15474974-T-C is described in Lovd as [Pathogenic].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4 link	c.529-23A>G	intron_variant	Intron 7 of 16	ENST00000383788.10	NP_005668.2	Q9Y215-1
COLQ	NM_080538.2 link	c.499-23A>G	intron_variant	Intron 7 of 16		NP_536799.1	Q9Y215-2
COLQ	NM_080539.4 link	c.427-23A>G	intron_variant	Intron 6 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.529-23A>G		intron_variant	Intron 7 of 16	1	NM_005677.4	ENSP00000373298.3		Q9Y215-1
COLQ	ENST00000603808.5 link	c.529-23A>G		intron_variant	Intron 7 of 16	1		ENSP00000474271.1		A0A0C4DGS2

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

GnomAD3 exomes

AF:

0.383

AC:

96300

AN:

251278

Hom.:

18828

AF XY:

0.385

AC XY:

52318

AN XY:

135800

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 SAS exome

AF:

0.388

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

Gnomad4 AFR exome

AF:

0.322

Gnomad4 AMR exome

AF:

0.336

Gnomad4 ASJ exome

AF:

0.464

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.390

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.396

Gnomad4 OTH exome

AF:

0.404

GnomAD4 genome

AF:

0.374

AC:

56820

AN:

152106

Hom.:

10770

Cov.:

AF XY:

0.374

AC XY:

27822

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.328

Gnomad4 AMR

AF:

0.369

Gnomad4 ASJ

AF:

0.471

Gnomad4 EAS

AF:

0.489

Gnomad4 SAS

AF:

0.381

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.403

Alfa

AF:

0.388

Hom.:

2537

Bravo

AF:

0.374

Asia WGS

AF:

0.368

AC:

1279

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

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. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

-0.49

CADD

Benign

DANN

Benign

0.74

BranchPoint Hunter

3.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over