NM_005677.4:c.*1395C>T

Variant names:

• chr3-15450249-G-A
• rs3274
• NM_005677.4:c.*1395C>T

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.*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
• Publications: 9 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]

ENSG00000293553 (HGNC:):

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

Our verdict: Benign. The variant received -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 VariationId 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.

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.*1395C>T		3_prime_UTR	Exon 17 of 17	NP_005668.2
	COLQ	NM_080538.2		c.*1395C>T		3_prime_UTR	Exon 17 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.*1395C>T		3_prime_UTR	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.*1395C>T		3_prime_UTR	Exon 17 of 17	ENSP00000373298.3	Q9Y215-1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*291+1196C>T		intron	N/A	ENSP00000518887.1	A0AAA9YHP9
	COLQ	ENST00000874202.1		c.*1395C>T		3_prime_UTR	Exon 17 of 17	ENSP00000544261.1

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

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 2 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.322 AC: 305 AN: 946

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.344 AC: 11 AN: 32

Other (OTH) AF: 0.333 AC: 4 AN: 12

GnomAD4 genome AF: 0.376 AC: 57188 AN: 151996 Hom.: 10818 Cov.: 32 AF XY: 0.375 AC XY: 27874 AN XY: 74270

African (AFR) AF: 0.339 AC: 14075 AN: 41464

American (AMR) AF: 0.371 AC: 5658 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.467 AC: 1621 AN: 3468

East Asian (EAS) AF: 0.490 AC: 2535 AN: 5174

South Asian (SAS) AF: 0.375 AC: 1806 AN: 4814

European-Finnish (FIN) AF: 0.335 AC: 3531 AN: 10544

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.390 AC: 26500 AN: 67952

Other (OTH) AF: 0.413 AC: 871 AN: 2110

Alfa AF: 0.387 Hom.: 43802

Bravo AF: 0.379

Asia WGS AF: 0.401 AC: 1391 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital myasthenic syndrome 5 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.51
PhyloP100		0.65
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: rs3274; hg19: chr3-15491756; COSMIC: COSV67526356; COSMIC: COSV67526356;