rs750387

Variant names:

• chr3-15479331-T-C
• rs750387
• NM_005677.4:c.366+7A>G

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.366+7A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 1,613,144 control chromosomes in the GnomAD database, including 1,203 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.042 (178 hom., cov: 32)
  • Exomes 𝑓: 0.036 (1025 hom.)
• Consequence: COLQ NM_005677.4 splice_region, intron
• Scores: Splicing: ADA: 0.00006183
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.315
• Publications: 8 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 3-15479331-T-C is Benign according to our data. Variant chr3-15479331-T-C is described in ClinVar as Benign. ClinVar VariationId is 128826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 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.366+7A>G		splice_region intron	N/A	NP_005668.2
	COLQ	NM_080538.2		c.336+7A>G		splice_region intron	N/A	NP_536799.1
	COLQ	NM_080539.4		c.264+7A>G		splice_region intron	N/A	NP_536800.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	ENST00000383788.10	TSL:1 MANE Select	c.366+7A>G		splice_region intron	N/A	ENSP00000373298.3
	COLQ	ENST00000603808.5	TSL:1	c.366+7A>G		splice_region intron	N/A	ENSP00000474271.1
	COLQ	ENST00000874202.1		c.366+7A>G		splice_region intron	N/A	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.0421 AC: 6413 AN: 152148 Hom.: 178 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.0197

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0389

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0257

Gnomad FIN AF: 0.0128

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0379

Gnomad OTH AF: 0.0545

GnomAD2 exomes AF: 0.0308 AC: 7745 AN: 251466 AF XY: 0.0317

Gnomad AFR exome AF: 0.0623

Gnomad AMR exome AF: 0.0221

Gnomad ASJ exome AF: 0.0319

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.0363

Gnomad OTH exome AF: 0.0391

GnomAD4 exome AF: 0.0356 AC: 51939 AN: 1460878 Hom.: 1025 Cov.: 31 AF XY: 0.0360 AC XY: 26131 AN XY: 726844

African (AFR) AF: 0.0656 AC: 2194 AN: 33444

American (AMR) AF: 0.0238 AC: 1063 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0348 AC: 910 AN: 26132

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39696

South Asian (SAS) AF: 0.0328 AC: 2827 AN: 86248

European-Finnish (FIN) AF: 0.0170 AC: 909 AN: 53420

Middle Eastern (MID) AF: 0.0710 AC: 409 AN: 5764

European-Non Finnish (NFE) AF: 0.0371 AC: 41185 AN: 1111098

Other (OTH) AF: 0.0404 AC: 2438 AN: 60352

GnomAD4 genome AF: 0.0422 AC: 6420 AN: 152266 Hom.: 178 Cov.: 32 AF XY: 0.0404 AC XY: 3012 AN XY: 74474

African (AFR) AF: 0.0644 AC: 2676 AN: 41546

American (AMR) AF: 0.0407 AC: 622 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0389 AC: 135 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4826

European-Finnish (FIN) AF: 0.0128 AC: 136 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0379 AC: 2577 AN: 68018

Other (OTH) AF: 0.0540 AC: 114 AN: 2112

Alfa AF: 0.0406 Hom.: 222

Bravo AF: 0.0444

Asia WGS AF: 0.0170 AC: 60 AN: 3478

EpiCase AF: 0.0422

EpiControl AF: 0.0442

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Congenital myasthenic syndrome 5 (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.65
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000062
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.11		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: rs750387; hg19: chr3-15520838;