Variant 3-15450249-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_005677.4(COLQ):c.*1395C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 152,990 control chromosomes in the GnomAD database, including 10,867 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 10818 hom., cov: 32)

Exomes 𝑓: 0.33 ( 49 hom. )

Consequence

COLQ
NM_005677.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.648

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:

EAF1 (HGNC:20907): (ELL associated factor 1) Enables transcription elongation regulator activity. Involved in regulation of transcription elongation from RNA polymerase II promoter. Located in intercellular bridge and nuclear body. Part of transcription elongation factor complex. [provided by Alliance of Genome Resources, Apr 2022]

EAF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-15450249-G-A is Benign according to our data. Variant chr3-15450249-G-A is described in ClinVar as [Benign]. Clinvar id is 343823.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
COLQ	NM_005677.4 linkuse as main transcript	c.*1395C>T	3_prime_UTR_variant	17/17	ENST00000383788.10
COLQ	NM_080538.2 linkuse as main transcript	c.*1395C>T	3_prime_UTR_variant	17/17
COLQ	NM_080539.4 linkuse as main transcript	c.*1395C>T	3_prime_UTR_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COLQ	ENST00000383788.10 linkuse as main transcript	c.*1395C>T		3_prime_UTR_variant	17/17	1	NM_005677.4	P4	Q9Y215-1

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57128

AN:

151878

Hom.:

10803

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.525

Gnomad AMR

AF:

0.371

Gnomad ASJ

AF:

0.467

Gnomad EAS

AF:

0.491

Gnomad SAS

AF:

0.374

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.392

Gnomad NFE

AF:

0.390

Gnomad OTH

AF:

0.407

GnomAD4 exome

AF:

0.326

AC:

324

AN:

994

Hom.:

Cov.:

AF XY:

0.330

AC XY:

182

AN XY:

552

show subpopulations

Gnomad4 AFR exome

AF:

1.00

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 FIN exome

AF:

0.322

Gnomad4 NFE exome

AF:

0.344

Gnomad4 OTH exome

AF:

0.333

GnomAD4 genome

AF:

0.376

AC:

57188

AN:

151996

Hom.:

10818

Cov.:

AF XY:

0.375

AC XY:

27874

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.371

Gnomad4 ASJ

AF:

0.467

Gnomad4 EAS

AF:

0.490

Gnomad4 SAS

AF:

0.375

Gnomad4 FIN

AF:

0.335

Gnomad4 NFE

AF:

0.390

Gnomad4 OTH

AF:

0.413

Alfa

AF:

0.389

Hom.:

18844

Bravo

AF:

0.379

Asia WGS

AF:

0.401

AC:

1391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 5

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

3.4

DANN

Benign

0.51

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

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