rs144158633

chr3-15477231-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_005677.4(COLQ):c.394-34C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,567,464 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0069 (10 hom., cov: 32)
  • Exomes 𝑓: 0.00076 (17 hom.)
• Consequence: COLQ NM_005677.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.568

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-15477231-G-A is Benign according to our data. Variant chr3-15477231-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 259858.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 = 0.00686 (1045/152290) while in subpopulation AFR AF= 0.0236 (981/41554). AF 95% confidence interval is 0.0224. There are 10 homozygotes in gnomad4. There are 492 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COLQ	NM_005677.4	c.394-34C>T		intron_variant		ENST00000383788.10
COLQ	NM_080538.2	c.364-34C>T		intron_variant
COLQ	NM_080539.4	c.292-34C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLQ	ENST00000383788.10	c.394-34C>T		intron_variant		1	NM_005677.4	P4

Frequencies

GnomAD3 genomes AF: 0.00676 AC: 1028 AN: 152172 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.0232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00295

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00162 AC: 307 AN: 189858 Hom.: 3 AF XY: 0.00126 AC XY: 128 AN XY: 101290

Gnomad AFR exome AF: 0.0217

Gnomad AMR exome AF: 0.00161

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000877

Gnomad OTH exome AF: 0.000403

GnomAD4 exome AF: 0.000764 AC: 1081 AN: 1415174 Hom.: 17 Cov.: 26 AF XY: 0.000683 AC XY: 479 AN XY: 701296

Gnomad4 AFR exome AF: 0.0247

Gnomad4 AMR exome AF: 0.00193

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000160

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000351

Gnomad4 OTH exome AF: 0.00223

GnomAD4 genome AF: 0.00686 AC: 1045 AN: 152290 Hom.: 10 Cov.: 32 AF XY: 0.00661 AC XY: 492 AN XY: 74458

Gnomad4 AFR AF: 0.0236

Gnomad4 AMR AF: 0.00294

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00371 Hom.: 0

Bravo AF: 0.00772

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.7
Dann	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs144158633; hg19: chr3-15518738;