rs17041264

Variant names:

• chr3-15521324-C-T
• rs17041264
• NM_005677.4:c.106+196G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005677.4(COLQ):​c.106+196G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0408 in 152,270 control chromosomes in the GnomAD database, including 292 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.041 (292 hom., cov: 32)
• Consequence: COLQ NM_005677.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.488
• Publications: 1 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 3-15521324-C-T is Benign according to our data. Variant chr3-15521324-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1192188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	NM_005677.4	MANE Select	c.106+196G>A		intron	N/A	NP_005668.2
	COLQ	NM_080539.4		c.106+196G>A		intron	N/A	NP_536800.2	Q9Y215-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	ENST00000383788.10	TSL:1 MANE Select	c.106+196G>A		intron	N/A	ENSP00000373298.3	Q9Y215-1
	COLQ	ENST00000603808.5	TSL:1	c.106+196G>A		intron	N/A	ENSP00000474271.1	A0A0C4DGS2
	COLQ	ENST00000874202.1		c.106+196G>A		intron	N/A	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.0407 AC: 6194 AN: 152150 Hom.: 288 Cov.: 32

Gnomad AFR AF: 0.00876

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.0175

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0363

Gnomad OTH AF: 0.0441

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0408 AC: 6206 AN: 152270 Hom.: 292 Cov.: 32 AF XY: 0.0429 AC XY: 3191 AN XY: 74456

African (AFR) AF: 0.00873 AC: 363 AN: 41564

American (AMR) AF: 0.135 AC: 2068 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3470

East Asian (EAS) AF: 0.104 AC: 536 AN: 5174

South Asian (SAS) AF: 0.0522 AC: 252 AN: 4824

European-Finnish (FIN) AF: 0.0175 AC: 186 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0363 AC: 2471 AN: 68008

Other (OTH) AF: 0.0441 AC: 93 AN: 2110

Alfa AF: 0.0376 Hom.: 82

Bravo AF: 0.0493

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.83
PhyloP100		-0.49
PromoterAI		-0.040	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17041264; hg19: chr3-15562831; COSMIC: COSV67529233;