chr3-15477224-G-C

Variant names:

• chr3-15477224-G-C
• rs2305612
• NM_005677.4:c.394-27C>G

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.44

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=-0.82).
• 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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4	c.394-27C>G		intron_variant	Intron 5 of 16	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.364-27C>G		intron_variant	Intron 5 of 16		NP_536799.1
COLQ	NM_080539.4	c.292-27C>G		intron_variant	Intron 4 of 15		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.394-27C>G		intron_variant	Intron 5 of 16	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5	c.394-27C>G		intron_variant	Intron 5 of 16	1		ENSP00000474271.1

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58651 AN: 151868 Hom.: 11471 Cov.: 31

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

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.: 29 AF XY: 0.401 AC XY: 284708 AN XY: 710446

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.: 31 AF XY: 0.386 AC XY: 28709 AN XY: 74298

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

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. -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

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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	-0.82
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

Other links and lift over

dbSNP: rs2305612; hg19: chr3-15518731; COSMIC: COSV67524883; COSMIC: COSV67524883;