chr3-15474287-T-C

Position:

• chr3-15474287-T-C

Variant summary

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

The ENST00000383788.10(COLQ):​c.556-15A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00451 in 1,613,546 control chromosomes in the GnomAD database, including 259 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.024 (134 hom., cov: 32)
  • Exomes 𝑓: 0.0025 (125 hom.)
• Consequence: COLQ ENST00000383788.10 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.01

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=-0.67).
• BP6: Variant 3-15474287-T-C is Benign according to our data. Variant chr3-15474287-T-C is described in ClinVar as [Benign]. Clinvar id is 259861.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLQ	NM_005677.4	c.556-15A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.526-15A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_536799.1
COLQ	NM_080539.4	c.454-15A>G		splice_polypyrimidine_tract_variant, intron_variant			NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.556-15A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_005677.4	ENSP00000373298	P4

Frequencies

GnomAD3 genomes AF: 0.0234 AC: 3568 AN: 152168 Hom.: 134 Cov.: 32

Gnomad AFR AF: 0.0803

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00981

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.0215

GnomAD3 exomes AF: 0.00628 AC: 1578 AN: 251370 Hom.: 62 AF XY: 0.00463 AC XY: 629 AN XY: 135856

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.00518

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.000326

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000220

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00253 AC: 3701 AN: 1461260 Hom.: 125 Cov.: 32 AF XY: 0.00221 AC XY: 1605 AN XY: 726978

Gnomad4 AFR exome AF: 0.0819

Gnomad4 AMR exome AF: 0.00543

Gnomad4 ASJ exome AF: 0.00517

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000134

Gnomad4 OTH exome AF: 0.00646

GnomAD4 genome AF: 0.0235 AC: 3583 AN: 152286 Hom.: 134 Cov.: 32 AF XY: 0.0223 AC XY: 1658 AN XY: 74472

Gnomad4 AFR AF: 0.0804

Gnomad4 AMR AF: 0.00980

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.0217

Alfa AF: 0.00323 Hom.: 5

Bravo AF: 0.0269

Asia WGS AF: 0.0250 AC: 88 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 20, 2016	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	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Congenital myasthenic syndrome 5 Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 30, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.86

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: rs57376327; hg19: chr3-15515794;