Variant rs2305616 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.600+40G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,611,564 control chromosomes in the GnomAD database, including 157,029 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16738 hom., cov: 31)

Exomes 𝑓: 0.44 ( 140291 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Splicing: ADA: 0.00007013

Clinical Significance

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

Conservation

PhyloP100: -1.31

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=-0.9).

BP6

Variant 3-15474188-C-T is Benign according to our data. Variant chr3-15474188-C-T is described in ClinVar as [Benign]. Clinvar id is 259862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-15474188-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
COLQ	NM_005677.4 linkuse as main transcript	c.600+40G>A	intron_variant	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2 linkuse as main transcript	c.570+40G>A	intron_variant		NP_536799.1
COLQ	NM_080539.4 linkuse as main transcript	c.498+40G>A	intron_variant		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10 linkuse as main transcript	c.600+40G>A		intron_variant		1	NM_005677.4	ENSP00000373298	P4	Q9Y215-1

Frequencies

GnomAD3 genomes

AF:

0.464

AC:

70467

AN:

151882

Hom.:

16717

Cov.:

show subpopulations

Gnomad AFR

AF:

0.556

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.433

Gnomad ASJ

AF:

0.516

Gnomad EAS

AF:

0.500

Gnomad SAS

AF:

0.409

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.427

Gnomad OTH

AF:

0.492

GnomAD3 exomes

AF:

0.428

AC:

107537

AN:

251300

Hom.:

23510

AF XY:

0.427

AC XY:

58059

AN XY:

135828

show subpopulations

Gnomad AFR exome

AF:

0.557

Gnomad AMR exome

AF:

0.364

Gnomad ASJ exome

AF:

0.504

Gnomad EAS exome

AF:

0.489

Gnomad SAS exome

AF:

0.421

Gnomad FIN exome

AF:

0.359

Gnomad NFE exome

AF:

0.427

Gnomad OTH exome

AF:

0.422

GnomAD4 exome

AF:

0.436

AC:

636338

AN:

1459564

Hom.:

140291

Cov.:

AF XY:

0.435

AC XY:

316272

AN XY:

726288

show subpopulations

Gnomad4 AFR exome

AF:

0.561

Gnomad4 AMR exome

AF:

0.372

Gnomad4 ASJ exome

AF:

0.506

Gnomad4 EAS exome

AF:

0.491

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.359

Gnomad4 NFE exome

AF:

0.434

Gnomad4 OTH exome

AF:

0.458

GnomAD4 genome

AF:

0.464

AC:

70540

AN:

152000

Hom.:

16738

Cov.:

AF XY:

0.461

AC XY:

34268

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.556

Gnomad4 AMR

AF:

0.433

Gnomad4 ASJ

AF:

0.516

Gnomad4 EAS

AF:

0.499

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.366

Gnomad4 NFE

AF:

0.427

Gnomad4 OTH

AF:

0.493

Alfa

AF:

0.440

Hom.:

5999

Bravo

AF:

0.474

Asia WGS

AF:

0.432

AC:

1499

AN:

3478

EpiCase

AF:

0.442

EpiControl

AF:

0.450

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	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.90

CADD

Benign

0.12

DANN

Benign

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000070

dbscSNV1_RF

Benign

0.0020

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