3-15451674-G-T

Variant names:

• chr3-15451674-G-T
• rs73818504
• NM_005677.4:c.1338C>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_005677.4(COLQ):​c.1338C>A​(p.Ile446Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00415 in 1,614,142 control chromosomes in the GnomAD database, including 198 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I446I) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.021 (89 hom., cov: 33)
  • Exomes 𝑓: 0.0024 (109 hom.)
• Consequence: COLQ NM_005677.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.58
• Publications: 1 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: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)

ENSG00000293553 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP6: Variant 3-15451674-G-T is Benign according to our data. Variant chr3-15451674-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 259855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.58 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0681 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	NM_005677.4	MANE Select	c.1338C>A	p.Ile446Ile	synonymous	Exon 17 of 17	NP_005668.2
	COLQ	NM_080538.2		c.1308C>A	p.Ile436Ile	synonymous	Exon 17 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.1236C>A	p.Ile412Ile	synonymous	Exon 16 of 16	NP_536800.2	Q9Y215-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLQ	ENST00000383788.10	TSL:1 MANE Select	c.1338C>A	p.Ile446Ile	synonymous	Exon 17 of 17	ENSP00000373298.3	Q9Y215-1
	COLQ	ENST00000603808.5	TSL:1	c.1341C>A	p.Ile447Ile	synonymous	Exon 17 of 17	ENSP00000474271.1	A0A0C4DGS2
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*62C>A		non_coding_transcript_exon	Exon 3 of 6	ENSP00000518887.1	A0AAA9YHP9

Frequencies

GnomAD3 genomes AF: 0.0209 AC: 3180 AN: 152180 Hom.: 89 Cov.: 33

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0122

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00582 AC: 1462 AN: 251324 AF XY: 0.00431

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.00509

Gnomad ASJ exome AF: 0.00437

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000414

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00241 AC: 3521 AN: 1461846 Hom.: 109 Cov.: 31 AF XY: 0.00217 AC XY: 1576 AN XY: 727220

African (AFR) AF: 0.0734 AC: 2456 AN: 33476

American (AMR) AF: 0.00586 AC: 262 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00509 AC: 133 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000185 AC: 16 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5764

European-Non Finnish (NFE) AF: 0.000260 AC: 289 AN: 1111996

Other (OTH) AF: 0.00550 AC: 332 AN: 60388

GnomAD4 genome AF: 0.0209 AC: 3185 AN: 152296 Hom.: 89 Cov.: 33 AF XY: 0.0207 AC XY: 1538 AN XY: 74468

African (AFR) AF: 0.0702 AC: 2917 AN: 41548

American (AMR) AF: 0.0122 AC: 186 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68036

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.00680 Hom.: 24

Bravo AF: 0.0241

Asia WGS AF: 0.00375 AC: 13 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Congenital myasthenic syndrome 5 (2)
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	5.0
DANN	Benign	0.79
PhyloP100		1.6
Mutation Taster		=97/3	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs73818504; hg19: chr3-15493181; COSMIC: COSV67525589; COSMIC: COSV67525589;