NM_005677.4:c.1298+35C>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• congenital myasthenic syndrome 5

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia

ENSG00000293553 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	NM_005677.4	MANE Select	c.1298+35C>A		intron	N/A	NP_005668.2
	COLQ	NM_080538.2		c.1268+35C>A		intron	N/A	NP_536799.1
	COLQ	NM_080539.4		c.1196+35C>A		intron	N/A	NP_536800.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	ENST00000383788.10	TSL:1 MANE Select	c.1298+35C>A		intron	N/A	ENSP00000373298.3
	COLQ	ENST00000603808.5	TSL:1	c.1301+35C>A		intron	N/A	ENSP00000474271.1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*22+35C>A		intron	N/A	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

GnomAD2 exomes AF: 0.0871 AC: 18078 AN: 207554 AF XY: 0.0775

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 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

African (AFR) AF: 0.249 AC: 6948 AN: 27892

American (AMR) AF: 0.214 AC: 8639 AN: 40288

Ashkenazi Jewish (ASJ) AF: 0.0530 AC: 1279 AN: 24134

East Asian (EAS) AF: 0.129 AC: 4709 AN: 36616

South Asian (SAS) AF: 0.0500 AC: 3846 AN: 76974

European-Finnish (FIN) AF: 0.0279 AC: 1425 AN: 51050

Middle Eastern (MID) AF: 0.0591 AC: 311 AN: 5264

European-Non Finnish (NFE) AF: 0.0454 AC: 40195 AN: 885278

Other (OTH) AF: 0.0663 AC: 3421 AN: 51566

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

African (AFR) AF: 0.242 AC: 10028 AN: 41384

American (AMR) AF: 0.168 AC: 2568 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0559 AC: 194 AN: 3468

East Asian (EAS) AF: 0.111 AC: 574 AN: 5154

South Asian (SAS) AF: 0.0503 AC: 242 AN: 4814

European-Finnish (FIN) AF: 0.0221 AC: 234 AN: 10608

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0464 AC: 3158 AN: 67988

Other (OTH) AF: 0.109 AC: 231 AN: 2112

Alfa AF: 0.0699 Hom.: 173

Bravo AF: 0.133

Asia WGS AF: 0.103 AC: 357 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.44
DANN	Benign	0.47
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1077827; hg19: chr3-15495301;