chr3-15475403-T-C

Variant names:

• chr3-15475403-T-C
• rs3816526
• NM_005677.4:c.528+22A>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.528+22A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 1,577,442 control chromosomes in the GnomAD database, including 123,100 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10763 hom., cov: 32)
  • Exomes 𝑓: 0.39 (112337 hom.)
• Consequence: COLQ NM_005677.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.209
• Publications: 9 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=-0.87).
• BP6: Variant 3-15475403-T-C is Benign according to our data. Variant chr3-15475403-T-C is described in ClinVar as Benign. ClinVar VariationId is 259859.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 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.528+22A>G		intron	N/A	NP_005668.2
	COLQ	NM_080538.2		c.498+22A>G		intron	N/A	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.426+22A>G		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.528+22A>G		intron	N/A	ENSP00000373298.3	Q9Y215-1
	COLQ	ENST00000603808.5	TSL:1	c.528+22A>G		intron	N/A	ENSP00000474271.1	A0A0C4DGS2
	COLQ	ENST00000874202.1		c.528+22A>G		intron	N/A	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56760 AN: 151914 Hom.: 10762 Cov.: 32

Gnomad AFR AF: 0.328

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.389

Gnomad OTH AF: 0.402

GnomAD2 exomes AF: 0.385 AC: 77877 AN: 202484 AF XY: 0.386

Gnomad AFR exome AF: 0.329

Gnomad AMR exome AF: 0.333

Gnomad ASJ exome AF: 0.463

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.393

Gnomad OTH exome AF: 0.379

GnomAD4 exome AF: 0.395 AC: 562713 AN: 1425410 Hom.: 112337 Cov.: 32 AF XY: 0.395 AC XY: 278474 AN XY: 705812

African (AFR) AF: 0.322 AC: 10587 AN: 32868

American (AMR) AF: 0.338 AC: 13712 AN: 40540

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 11793 AN: 25444

East Asian (EAS) AF: 0.482 AC: 18609 AN: 38644

South Asian (SAS) AF: 0.389 AC: 31835 AN: 81762

European-Finnish (FIN) AF: 0.342 AC: 17507 AN: 51186

Middle Eastern (MID) AF: 0.391 AC: 1997 AN: 5102

European-Non Finnish (NFE) AF: 0.397 AC: 432831 AN: 1090956

Other (OTH) AF: 0.405 AC: 23842 AN: 58908

GnomAD4 genome AF: 0.374 AC: 56785 AN: 152032 Hom.: 10763 Cov.: 32 AF XY: 0.374 AC XY: 27775 AN XY: 74280

African (AFR) AF: 0.328 AC: 13598 AN: 41496

American (AMR) AF: 0.369 AC: 5631 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1635 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2519 AN: 5152

South Asian (SAS) AF: 0.382 AC: 1840 AN: 4818

European-Finnish (FIN) AF: 0.352 AC: 3718 AN: 10548

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.389 AC: 26412 AN: 67970

Other (OTH) AF: 0.402 AC: 848 AN: 2108

Alfa AF: 0.388 Hom.: 15477

Bravo AF: 0.374

Asia WGS AF: 0.369 AC: 1281 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital myasthenic syndrome 5 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.46
PhyloP100		-0.21
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: rs3816526; hg19: chr3-15516910; COSMIC: COSV67524177; COSMIC: COSV67524177;