3-15475403-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005677.4(COLQ):c.528+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,577,442 control chromosomes in the GnomAD database, including 123,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10763 hom., cov: 32)

Exomes 𝑓: 0.39 ( 112337 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.209

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-15475403-T-C is Benign according to our data. Variant chr3-15475403-T-C is described in ClinVar as [Benign]. Clinvar id is 259859.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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4 link	c.528+22A>G	intron_variant	Intron 7 of 16	ENST00000383788.10	NP_005668.2	Q9Y215-1
COLQ	NM_080538.2 link	c.498+22A>G	intron_variant	Intron 7 of 16		NP_536799.1	Q9Y215-2
COLQ	NM_080539.4 link	c.426+22A>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.528+22A>G		intron_variant	Intron 7 of 16	1	NM_005677.4	ENSP00000373298.3		Q9Y215-1
COLQ	ENST00000603808.5 link	c.528+22A>G		intron_variant	Intron 7 of 16	1		ENSP00000474271.1		A0A0C4DGS2

Frequencies

GnomAD3 genomes

AF:

0.374

AC:

56760

AN:

151914

Hom.:

10762

Cov.:

show subpopulations

Gnomad AFR

AF:

0.328

Gnomad AMI

AF:

0.524

Gnomad AMR

AF:

0.369

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:

0.385

AC:

77877

AN:

202484

Hom.:

15145

AF XY:

0.386

AC XY:

41743

AN XY:

108018

show subpopulations

Gnomad AFR exome

AF:

0.329

Gnomad AMR exome

AF:

0.333

Gnomad ASJ exome

AF:

0.463

Gnomad EAS exome

AF:

0.479

Gnomad SAS exome

AF:

0.387

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.393

Gnomad OTH exome

AF:

0.379

GnomAD4 exome

AF:

0.395

AC:

562713

AN:

1425410

Hom.:

112337

Cov.:

AF XY:

0.395

AC XY:

278474

AN XY:

705812

show subpopulations

Gnomad4 AFR exome

AF:

0.322

Gnomad4 AMR exome

AF:

0.338

Gnomad4 ASJ exome

AF:

0.463

Gnomad4 EAS exome

AF:

0.482

Gnomad4 SAS exome

AF:

0.389

Gnomad4 FIN exome

AF:

0.342

Gnomad4 NFE exome

AF:

0.397

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.374

AC:

56785

AN:

152032

Hom.:

10763

Cov.:

AF XY:

0.374

AC XY:

27775

AN XY:

74280

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:

0.382

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.402

Alfa

AF:

0.392

Hom.:

12193

Bravo

AF:

0.374

Asia WGS

AF:

0.369

AC:

1281

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

-0.87

CADD

Benign

1.5

DANN

Benign

0.46

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

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