3-15451129-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005677.4(COLQ):c.*515C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0625 in 164,430 control chromosomes in the GnomAD database, including 577 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (560 hom., cov: 31)
  • Exomes 𝑓: 0.031 (17 hom.)
• Consequence: COLQ NM_005677.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 3-15451129-G-A is Benign according to our data. Variant chr3-15451129-G-A is described in ClinVar as [Benign]. Clinvar id is 343835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLQ	NM_005677.4	c.*515C>T		3_prime_UTR_variant	17/17	ENST00000383788.10
COLQ	NM_080538.2	c.*515C>T		3_prime_UTR_variant	17/17
COLQ	NM_080539.4	c.*515C>T		3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLQ	ENST00000383788.10	c.*515C>T		3_prime_UTR_variant	17/17	1	NM_005677.4	P4

Frequencies

GnomAD3 genomes AF: 0.0650 AC: 9879 AN: 151988 Hom.: 559 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0499

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.0126

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0357

Gnomad OTH AF: 0.0684

GnomAD4 exome AF: 0.0315 AC: 388 AN: 12324 Hom.: 17 Cov.: 0 AF XY: 0.0323 AC XY: 215 AN XY: 6660

Gnomad4 AFR exome AF: 0.174

Gnomad4 AMR exome AF: 0.0268

Gnomad4 ASJ exome AF: 0.00575

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0364

Gnomad4 FIN exome AF: 0.0139

Gnomad4 NFE exome AF: 0.0311

Gnomad4 OTH exome AF: 0.0257

GnomAD4 genome AF: 0.0650 AC: 9891 AN: 152106 Hom.: 560 Cov.: 31 AF XY: 0.0626 AC XY: 4652 AN XY: 74352

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0499

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0244

Gnomad4 FIN AF: 0.0126

Gnomad4 NFE AF: 0.0357

Gnomad4 OTH AF: 0.0676

Alfa AF: 0.0414 Hom.: 197

Bravo AF: 0.0718

Asia WGS AF: 0.0180 AC: 62 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital myasthenic syndrome 5 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.55
Dann	Benign	0.62

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

Other links and lift over

dbSNP: rs10154896; hg19: chr3-15492636;