Variant 3-15477224-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 259857.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-15477224-G-C is described in Lovd as [Pathogenic].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COLQ	NM_005677.4 linkuse as main transcript	c.394-27C>G	intron_variant	ENST00000383788.10
COLQ	NM_080538.2 linkuse as main transcript	c.364-27C>G	intron_variant
COLQ	NM_080539.4 linkuse as main transcript	c.292-27C>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLQ	ENST00000383788.10 linkuse as main transcript	c.394-27C>G		intron_variant		1	NM_005677.4	P4	Q9Y215-1

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

GnomAD3 exomes

AF:

0.397

AC:

82162

AN:

207136

Hom.:

16193

AF XY:

0.399

AC XY:

44303

AN XY:

111052

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 SAS exome

AF:

0.393

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

Gnomad4 AFR exome

AF:

0.352

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.467

Gnomad4 EAS exome

AF:

0.502

Gnomad4 SAS exome

AF:

0.393

Gnomad4 FIN exome

AF:

0.343

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.415

GnomAD4 genome

AF:

0.386

AC:

58701

AN:

151986

Hom.:

11482

Cov.:

AF XY:

0.386

AC XY:

28709

AN XY:

74298

show subpopulations

Gnomad4 AFR

AF:

0.355

Gnomad4 AMR

AF:

0.380

Gnomad4 ASJ

AF:

0.474

Gnomad4 EAS

AF:

0.518

Gnomad4 SAS

AF:

0.386

Gnomad4 FIN

AF:

0.353

Gnomad4 NFE

AF:

0.394

Gnomad4 OTH

AF:

0.419

Alfa

AF:

0.397

Hom.:

2222

Bravo

AF:

0.388

Asia WGS

AF:

0.400

AC:

1391

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	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. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Congenital myasthenic syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 30, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.9

DANN

Benign

0.58

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

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