rs1077827

Variant names:

• chr3-15453794-G-T
• rs1077827
• NM_005677.4:c.1298+35C>A

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.1298+35C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0652 in 1,351,064 control chromosomes in the GnomAD database, including 5,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1619 hom., cov: 32)
  • Exomes 𝑓: 0.059 (3470 hom.)
• Consequence: COLQ NM_005677.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.310

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)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-15453794-G-T is Benign according to our data. Variant chr3-15453794-G-T is described in ClinVar as [Benign]. Clinvar id is 259853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
COLQ	NM_005677.4	c.1298+35C>A		intron_variant	Intron 16 of 16	ENST00000383788.10	NP_005668.2
COLQ	NM_080538.2	c.1268+35C>A		intron_variant	Intron 16 of 16		NP_536799.1
COLQ	NM_080539.4	c.1196+35C>A		intron_variant	Intron 15 of 15		NP_536800.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
COLQ	ENST00000383788.10	c.1298+35C>A		intron_variant	Intron 16 of 16	1	NM_005677.4	ENSP00000373298.3
COLQ	ENST00000603808.5	c.1301+35C>A		intron_variant	Intron 16 of 16	1		ENSP00000474271.1
EAF1-AS1	ENST00000629729.2	n.145+35C>A		intron_variant	Intron 2 of 5	5		ENSP00000518887.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17219 AN: 151884 Hom.: 1606 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0509

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0464

Gnomad OTH AF: 0.109

GnomAD3 exomes AF: 0.0871 AC: 18078 AN: 207554 Hom.: 1426 AF XY: 0.0775 AC XY: 8613 AN XY: 111198

Gnomad AFR exome AF: 0.247

Gnomad AMR exome AF: 0.218

Gnomad ASJ exome AF: 0.0557

Gnomad EAS exome AF: 0.115

Gnomad SAS exome AF: 0.0511

Gnomad FIN exome AF: 0.0255

Gnomad NFE exome AF: 0.0442

Gnomad OTH exome AF: 0.0730

GnomAD4 exome AF: 0.0590 AC: 70773 AN: 1199062 Hom.: 3470 Cov.: 16 AF XY: 0.0576 AC XY: 34925 AN XY: 605946

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.214

Gnomad4 ASJ exome AF: 0.0530

Gnomad4 EAS exome AF: 0.129

Gnomad4 SAS exome AF: 0.0500

Gnomad4 FIN exome AF: 0.0279

Gnomad4 NFE exome AF: 0.0454

Gnomad4 OTH exome AF: 0.0663

GnomAD4 genome AF: 0.114 AC: 17270 AN: 152002 Hom.: 1619 Cov.: 32 AF XY: 0.113 AC XY: 8404 AN XY: 74312

Gnomad4 AFR AF: 0.242

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0503

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.0464

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0699 Hom.: 173

Bravo AF: 0.133

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.47

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: rs1077827; hg19: chr3-15495301;