Variant rs111284326 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_005677.4(COLQ):c.1299-31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00185 in 1,589,434 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0093 ( 24 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 22 hom. )

Consequence

COLQ
NM_005677.4 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.314

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 3-15451744-C-T is Benign according to our data. Variant chr3-15451744-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259854.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 = 0.00933 (1421/152340) while in subpopulation AFR AF= 0.0324 (1348/41584). AF 95% confidence interval is 0.031. There are 24 homozygotes in gnomad4. There are 674 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
COLQ	NM_005677.4 linkuse as main transcript	c.1299-31G>A	intron_variant	ENST00000383788.10
COLQ	NM_080538.2 linkuse as main transcript	c.1269-31G>A	intron_variant
COLQ	NM_080539.4 linkuse as main transcript	c.1197-31G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLQ	ENST00000383788.10 linkuse as main transcript	c.1299-31G>A		intron_variant		1	NM_005677.4	P4	Q9Y215-1

Frequencies

GnomAD3 genomes

AF:

0.00923

AC:

1405

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0321

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00716

GnomAD3 exomes

AF:

0.00244

AC:

609

AN:

249446

Hom.:

AF XY:

0.00175

AC XY:

237

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.0328

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.000298

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000143

Gnomad OTH exome

AF:

0.000980

GnomAD4 exome

AF:

0.00106

AC:

1518

AN:

1437094

Hom.:

Cov.:

AF XY:

0.000911

AC XY:

653

AN XY:

716412

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.000269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000105

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000106

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00933

AC:

1421

AN:

152340

Hom.:

Cov.:

AF XY:

0.00905

AC XY:

674

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0324

Gnomad4 AMR

AF:

0.00288

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00709

Alfa

AF:

0.00477

Hom.:

Bravo

AF:

0.0106

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 17, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.9

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over