3-15450249-G-A

Variant names:

• chr3-15450249-G-A
• rs3274
• NM_005677.4:c.*1395C>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.*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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.648

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]

EAF1-AS1 (HGNC:42328): (EAF1 antisense RNA 1)

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]

ACMG classification

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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4	c.*1395C>T		3_prime_UTR_variant	Exon 17 of 17	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.*1395C>T		3_prime_UTR_variant	Exon 17 of 17		NP_536799.1
COLQ	NM_080539.4	c.*1395C>T		3_prime_UTR_variant	Exon 16 of 16		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788	c.*1395C>T		3_prime_UTR_variant	Exon 17 of 17	1	NM_005677.4	ENSP00000373298.3
EAF1-AS1	ENST00000629729.2	n.414+1196C>T		intron_variant	Intron 3 of 5	5		ENSP00000518887.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57128 AN: 151878 Hom.: 10803 Cov.: 32

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.: 49 Cov.: 0 AF XY: 0.330 AC XY: 182 AN XY: 552

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.: 32 AF XY: 0.375 AC XY: 27874 AN XY: 74270

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

Submissions by phenotype

Congenital myasthenic syndrome 5 Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

Other links and lift over

dbSNP: rs3274; hg19: chr3-15491756; COSMIC: COSV67526356; COSMIC: COSV67526356;