rs2305616

chr3-15474188-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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:3
• Conservation: PhyloP100: -1.31

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
COLQ	NM_005677.4	c.600+40G>A		intron_variant		ENST00000383788.10
COLQ	NM_080538.2	c.570+40G>A		intron_variant
COLQ	NM_080539.4	c.498+40G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLQ	ENST00000383788.10	c.600+40G>A		intron_variant		1	NM_005677.4	P4

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70467 AN: 151882 Hom.: 16717 Cov.: 31

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

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.: 32 AF XY: 0.435 AC XY: 316272 AN XY: 726288

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.: 31 AF XY: 0.461 AC XY: 34268 AN XY: 74272

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:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

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. -

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

Other links and lift over

dbSNP: rs2305616; hg19: chr3-15515695; COSMIC: COSV67524641; COSMIC: COSV67524641;