NM_005677.4:c.*1001G>A

Variant names:

• chr3-15450643-C-T
• rs3846128
• NM_005677.4:c.*1001G>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.*1001G>A 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 153,132 control chromosomes in the GnomAD database, including 10,886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (10820 hom., cov: 32)
  • Exomes 𝑓: 0.35 (66 hom.)
• Consequence: COLQ NM_005677.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.962
• Publications: 5 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=-0.81).
• BP6: Variant 3-15450643-C-T is Benign according to our data. Variant chr3-15450643-C-T is described in ClinVar as Benign. ClinVar VariationId is 343828.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.*1001G>A		3_prime_UTR	Exon 17 of 17	NP_005668.2
	COLQ	NM_080538.2		c.*1001G>A		3_prime_UTR	Exon 17 of 17	NP_536799.1	Q9Y215-2
	COLQ	NM_080539.4		c.*1001G>A		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.*1001G>A		3_prime_UTR	Exon 17 of 17	ENSP00000373298.3	Q9Y215-1
	ENSG00000293553	ENST00000629729.3	TSL:5	n.*291+802G>A		intron	N/A	ENSP00000518887.1	A0AAA9YHP9
	COLQ	ENST00000874202.1		c.*1001G>A		3_prime_UTR	Exon 17 of 17	ENSP00000544261.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57132 AN: 151866 Hom.: 10805 Cov.: 32

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.490

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.390

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.348 AC: 399 AN: 1148 Hom.: 66 Cov.: 0 AF XY: 0.343 AC XY: 215 AN XY: 626

African (AFR) AF: 0.250 AC: 2 AN: 8

American (AMR) AC: 0 AN: 0

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

East Asian (EAS) AF: 0.750 AC: 3 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.341 AC: 336 AN: 986

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.418 AC: 56 AN: 134

Other (OTH) AF: 0.00 AC: 0 AN: 12

GnomAD4 genome AF: 0.376 AC: 57192 AN: 151984 Hom.: 10820 Cov.: 32 AF XY: 0.375 AC XY: 27879 AN XY: 74292

African (AFR) AF: 0.340 AC: 14070 AN: 41440

American (AMR) AF: 0.371 AC: 5662 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1620 AN: 3464

East Asian (EAS) AF: 0.490 AC: 2524 AN: 5154

South Asian (SAS) AF: 0.375 AC: 1810 AN: 4822

European-Finnish (FIN) AF: 0.335 AC: 3539 AN: 10564

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

European-Non Finnish (NFE) AF: 0.390 AC: 26505 AN: 67960

Other (OTH) AF: 0.414 AC: 871 AN: 2104

Alfa AF: 0.374 Hom.: 1351

Bravo AF: 0.379

Asia WGS AF: 0.400 AC: 1390 AN: 3478

ClinVar

ClinVar submissions

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	-0.81
CADD	Benign	8.9
DANN	Benign	0.42
PhyloP100		0.96
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: rs3846128; hg19: chr3-15492150; COSMIC: COSV67525620; COSMIC: COSV67525620;