rs200529572

Positions:

• chr3-15489656-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005677.4(COLQ):​c.107-19G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00213 in 1,610,092 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (5 hom.)
• Consequence: COLQ NM_005677.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.865

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=-0.64).
• BP6: Variant 3-15489656-C-T is Benign according to our data. Variant chr3-15489656-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-15489656-C-T is described in Lovd as [Likely_benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0014 (213/152340) while in subpopulation NFE AF= 0.00193 (131/68032). AF 95% confidence interval is 0.00166. There are 0 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLQ	NM_005677.4	c.107-19G>A		intron_variant		ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.77-19G>A		intron_variant			NP_536799.1
COLQ	NM_080539.4	c.107-19G>A		intron_variant			NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.107-19G>A		intron_variant		1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5	c.107-19G>A		intron_variant		1		ENSP00000474271.1

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152222 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000603

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00169 AC: 417 AN: 246474 Hom.: 2 AF XY: 0.00185 AC XY: 246 AN XY: 133328

Gnomad AFR exome AF: 0.000692

Gnomad AMR exome AF: 0.000614

Gnomad ASJ exome AF: 0.00111

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00232

Gnomad FIN exome AF: 0.000616

Gnomad NFE exome AF: 0.00252

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00220 AC: 3213 AN: 1457752 Hom.: 5 Cov.: 30 AF XY: 0.00217 AC XY: 1576 AN XY: 725232

Gnomad4 AFR exome AF: 0.000210

Gnomad4 AMR exome AF: 0.000562

Gnomad4 ASJ exome AF: 0.00119

Gnomad4 EAS exome AF: 0.0000505

Gnomad4 SAS exome AF: 0.00249

Gnomad4 FIN exome AF: 0.000863

Gnomad4 NFE exome AF: 0.00251

Gnomad4 OTH exome AF: 0.00171

GnomAD4 genome AF: 0.00140 AC: 213 AN: 152340 Hom.: 0 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74488

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00115

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00125

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.00150

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 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. -
Likely 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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

not provided Benign:1

Likely 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	-0.64
CADD	Benign	6.1
DANN	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs200529572; hg19: chr3-15531163;