rs17041264

Positions:

• chr3-15521324-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.76).
• 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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
COLQ	NM_005677.4	c.106+196G>A		intron_variant		ENST00000383788.10	NP_005668.2
COLQ	NM_080539.4	c.106+196G>A		intron_variant			NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.106+196G>A		intron_variant		1	NM_005677.4	ENSP00000373298	P4

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

Gnomad4 AFR AF: 0.00873

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0522

Gnomad4 FIN AF: 0.0175

Gnomad4 NFE AF: 0.0363

Gnomad4 OTH AF: 0.0441

Alfa AF: 0.0377 Hom.: 74

Bravo AF: 0.0493

Asia WGS AF: 0.0660 AC: 228 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 28, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.83

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

Publications

LitVar

Other links and lift over

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