Variant 3-15451279-T-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.*365A>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 0.433 in 356,538 control chromosomes in the GnomAD database, including 33,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 14842 hom., cov: 31)

Exomes 𝑓: 0.43 ( 18926 hom. )

Consequence

COLQ
NM_005677.4 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.550

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=-0.94).

BP6

Variant 3-15451279-T-A is Benign according to our data. Variant chr3-15451279-T-A is described in ClinVar as [Benign]. Clinvar id is 343839.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
COLQ	NM_005677.4 linkuse as main transcript	c.*365A>T	3_prime_UTR_variant	17/17	ENST00000383788.10
COLQ	NM_080538.2 linkuse as main transcript	c.*365A>T	3_prime_UTR_variant	17/17
COLQ	NM_080539.4 linkuse as main transcript	c.*365A>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.*365A>T		3_prime_UTR_variant	17/17	1	NM_005677.4	P4	Q9Y215-1

Frequencies

GnomAD3 genomes

AF:

0.442

AC:

67110

AN:

151710

Hom.:

14816

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.486

Gnomad EAS

AF:

0.492

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.349

Gnomad MID

AF:

0.446

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.476

GnomAD4 exome

AF:

0.425

AC:

87069

AN:

204710

Hom.:

18926

Cov.:

AF XY:

0.425

AC XY:

46417

AN XY:

109282

show subpopulations

Gnomad4 AFR exome

AF:

0.494

Gnomad4 AMR exome

AF:

0.383

Gnomad4 ASJ exome

AF:

0.486

Gnomad4 EAS exome

AF:

0.486

Gnomad4 SAS exome

AF:

0.424

Gnomad4 FIN exome

AF:

0.341

Gnomad4 NFE exome

AF:

0.423

Gnomad4 OTH exome

AF:

0.442

GnomAD4 genome

AF:

0.443

AC:

67186

AN:

151828

Hom.:

14842

Cov.:

AF XY:

0.439

AC XY:

32591

AN XY:

74206

show subpopulations

Gnomad4 AFR

AF:

0.491

Gnomad4 AMR

AF:

0.421

Gnomad4 ASJ

AF:

0.486

Gnomad4 EAS

AF:

0.491

Gnomad4 SAS

AF:

0.411

Gnomad4 FIN

AF:

0.349

Gnomad4 NFE

AF:

0.426

Gnomad4 OTH

AF:

0.482

Alfa

AF:

0.426

Hom.:

1746

Bravo

AF:

0.451

Asia WGS

AF:

0.420

AC:

1457

AN:

3476

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

-0.94

CADD

Benign

1.5

DANN

Benign

0.44

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