chr3-15489656-C-T

Variant names:

• chr3-15489656-C-T
• rs200529572
• NM_005677.4:c.107-19G>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.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
• 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: 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=-0.64).
• BP6: Variant 3-15489656-C-T is Benign according to our data. Variant chr3-15489656-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259849.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	NM_005677.4	MANE Select	c.107-19G>A		intron	N/A	NP_005668.2
	COLQ	NM_080538.2		c.77-19G>A		intron	N/A	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.107-19G>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.107-19G>A		intron	N/A	ENSP00000373298.3	Q9Y215-1
	COLQ	ENST00000603808.5	TSL:1	c.107-19G>A		intron	N/A	ENSP00000474271.1	A0A0C4DGS2
	COLQ	ENST00000874202.1		c.107-19G>A		intron	N/A	ENSP00000544261.1

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

GnomAD2 exomes AF: 0.00169 AC: 417 AN: 246474 AF XY: 0.00185

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 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

African (AFR) AF: 0.000210 AC: 7 AN: 33402

American (AMR) AF: 0.000562 AC: 25 AN: 44512

Ashkenazi Jewish (ASJ) AF: 0.00119 AC: 31 AN: 26064

East Asian (EAS) AF: 0.0000505 AC: 2 AN: 39632

South Asian (SAS) AF: 0.00249 AC: 214 AN: 85862

European-Finnish (FIN) AF: 0.000863 AC: 46 AN: 53290

Middle Eastern (MID) AF: 0.000718 AC: 4 AN: 5574

European-Non Finnish (NFE) AF: 0.00251 AC: 2781 AN: 1109212

Other (OTH) AF: 0.00171 AC: 103 AN: 60204

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

African (AFR) AF: 0.000601 AC: 25 AN: 41576

American (AMR) AF: 0.00111 AC: 17 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00125 AC: 6 AN: 4818

European-Finnish (FIN) AF: 0.000282 AC: 3 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68032

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00169 Hom.: 0

Bravo AF: 0.00150

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	6.1
DANN	Benign	0.87
PhyloP100		-0.86
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200529572; hg19: chr3-15531163;