rs111284326

Variant names:

• chr3-15451744-C-T
• rs111284326
• NM_005677.4:c.1299-31G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005677.4(COLQ):​c.1299-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,589,434 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0093 (24 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (22 hom.)
• Consequence: COLQ NM_005677.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.314
• Publications: 0 publications found

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]

COLQ Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 5

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia

ENSG00000293553 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-15451744-C-T is Benign according to our data. Variant chr3-15451744-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 259854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00933 (1421/152340) while in subpopulation AFR AF = 0.0324 (1348/41584). AF 95% confidence interval is 0.031. There are 24 homozygotes in GnomAd4. There are 674 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 24 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	NM_005677.4	MANE Select	c.1299-31G>A		intron	N/A	NP_005668.2
	COLQ	NM_080538.2		c.1269-31G>A		intron	N/A	NP_536799.1
	COLQ	NM_080539.4		c.1197-31G>A		intron	N/A	NP_536800.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	ENST00000383788.10	TSL:1 MANE Select	c.1299-31G>A		intron	N/A	ENSP00000373298.3
	COLQ	ENST00000603808.5	TSL:1	c.1302-31G>A		intron	N/A	ENSP00000474271.1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*23-31G>A		intron	N/A	ENSP00000518887.1

Frequencies

GnomAD3 genomes AF: 0.00923 AC: 1405 AN: 152222 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00716

GnomAD2 exomes AF: 0.00244 AC: 609 AN: 249446 AF XY: 0.00175

Gnomad AFR exome AF: 0.0328

Gnomad AMR exome AF: 0.00153

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000143

Gnomad OTH exome AF: 0.000980

GnomAD4 exome AF: 0.00106 AC: 1518 AN: 1437094 Hom.: 22 Cov.: 26 AF XY: 0.000911 AC XY: 653 AN XY: 716412

African (AFR) AF: 0.0344 AC: 1133 AN: 32936

American (AMR) AF: 0.00157 AC: 70 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.000269 AC: 7 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39566

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85726

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53252

Middle Eastern (MID) AF: 0.00290 AC: 15 AN: 5166

European-Non Finnish (NFE) AF: 0.000106 AC: 116 AN: 1090198

Other (OTH) AF: 0.00282 AC: 168 AN: 59552

GnomAD4 genome AF: 0.00933 AC: 1421 AN: 152340 Hom.: 24 Cov.: 33 AF XY: 0.00905 AC XY: 674 AN XY: 74496

African (AFR) AF: 0.0324 AC: 1348 AN: 41584

American (AMR) AF: 0.00288 AC: 44 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68032

Other (OTH) AF: 0.00709 AC: 15 AN: 2116

Alfa AF: 0.00474 Hom.: 2

Bravo AF: 0.0106

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.9
DANN	Benign	0.77
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs111284326; hg19: chr3-15493251;