NM_000080.4:c.*43T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000080.4(CHRNE):c.*43T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,589,882 control chromosomes in the GnomAD database, including 459 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 219 hom., cov: 33)

Exomes 𝑓: 0.0055 ( 240 hom. )

Consequence

CHRNE
NM_000080.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.92

Publications

2 publications found

Variant links:

Genes affected

CHRNE (HGNC:1966): (cholinergic receptor nicotinic epsilon subunit) Acetylcholine receptors at mature mammalian neuromuscular junctions are pentameric protein complexes composed of four subunits in the ratio of two alpha subunits to one beta, one epsilon, and one delta subunit. The acetylcholine receptor changes subunit composition shortly after birth when the epsilon subunit replaces the gamma subunit seen in embryonic receptors. Mutations in the epsilon subunit are associated with congenital myasthenic syndrome. [provided by RefSeq, Sep 2009]

CHRNE Gene-Disease associations (from GenCC):

congenital myasthenic syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
congenital myasthenic syndrome 4A
Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4B
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4C
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 17-4898693-A-G is Benign according to our data. Variant chr17-4898693-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254885.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4 link	c.*43T>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000649488.2	NP_000071.1	Q04844
CHRNE	XM_017024115.2 link	c.*43T>C		3_prime_UTR_variant	Exon 13 of 13		XP_016879604.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CHRNE	ENST00000649488.2 link	c.*43T>C	3_prime_UTR_variant	Exon 12 of 12		NM_000080.4	ENSP00000497829.1	Q04844
CHRNE	ENST00000572438.1 link	n.1211T>C	non_coding_transcript_exon_variant	Exon 7 of 7	5
CHRNE	ENST00000652550.1 link	n.1251T>C	non_coding_transcript_exon_variant	Exon 4 of 4
CHRNE	ENST00000649830.1 link	c.*161T>C	3_prime_UTR_variant	Exon 11 of 11			ENSP00000496907.1	A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4975

AN:

152024

Hom.:

219

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0187

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.00254

Gnomad OTH

AF:

0.0325

GnomAD2 exomes

AF:

0.0107

AC:

2273

AN:

212434

AF XY:

0.00878

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0109

Gnomad ASJ exome

AF:

0.0218

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00266

Gnomad OTH exome

AF:

0.0145

GnomAD4 exome

AF:

0.00551

AC:

7928

AN:

1437740

Hom.:

240

Cov.:

AF XY:

0.00509

AC XY:

3629

AN XY:

712758

show subpopulations

African (AFR)

AF:

0.112

AC:

3738

AN:

33314

American (AMR)

AF:

0.0121

AC:

484

AN:

39916

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

590

AN:

25542

East Asian (EAS)

AF:

0.00

AC:

AN:

38962

South Asian (SAS)

AF:

0.000460

AC:

AN:

82626

European-Finnish (FIN)

AF:

0.0000789

AC:

AN:

50684

Middle Eastern (MID)

AF:

0.0179

AC:

102

AN:

5712

European-Non Finnish (NFE)

AF:

0.00202

AC:

2226

AN:

1101358

Other (OTH)

AF:

0.0125

AC:

746

AN:

59626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

451

902

1352

1803

2254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0328

AC:

4983

AN:

152142

Hom.:

219

Cov.:

AF XY:

0.0316

AC XY:

2350

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.105

AC:

4363

AN:

41502

American (AMR)

AF:

0.0187

AC:

285

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00255

AC:

173

AN:

67970

Other (OTH)

AF:

0.0322

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

234

468

701

935

1169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.0374

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital myasthenic syndrome

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.14

(source)

DANN

Benign

0.24

PhyloP100

-3.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over