rs56377005

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000080.4(CHRNE):c.966C>T(p.Cys322Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,603,594 control chromosomes in the GnomAD database, including 351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 31 hom., cov: 32)

Exomes 𝑓: 0.015 ( 320 hom. )

Consequence

CHRNE
NM_000080.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.240

Publications

7 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 links:

C17orf107 (HGNC:37238): (chromosome 17 open reading frame 107)

C17orf107 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-4899534-G-A is Benign according to our data. Variant chr17-4899534-G-A is described in ClinVar as Benign. ClinVar VariationId is 254904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.24 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4 link	c.966C>T	p.Cys322Cys	synonymous_variant	Exon 9 of 12	ENST00000649488.2	NP_000071.1
C17orf107	NM_001145536.2 link	c.-229G>A		upstream_gene_variant		ENST00000381365.4	NP_001139008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649488.2 link	c.966C>T	p.Cys322Cys	synonymous_variant	Exon 9 of 12		NM_000080.4	ENSP00000497829.1
C17orf107	ENST00000381365.4 link	c.-229G>A		upstream_gene_variant		2	NM_001145536.2	ENSP00000370770.3

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1829

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0522

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0172

GnomAD2 exomes

AF:

0.0173

AC:

4005

AN:

231336

AF XY:

0.0195

show subpopulations

Gnomad AFR exome

AF:

0.00193

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0392

Gnomad EAS exome

AF:

0.000230

Gnomad FIN exome

AF:

0.00583

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0148

AC:

21434

AN:

1451290

Hom.:

320

Cov.:

AF XY:

0.0162

AC XY:

11641

AN XY:

720620

show subpopulations

African (AFR)

AF:

0.00183

AC:

AN:

33390

American (AMR)

AF:

0.0105

AC:

454

AN:

43378

Ashkenazi Jewish (ASJ)

AF:

0.0389

AC:

1001

AN:

25756

East Asian (EAS)

AF:

0.000127

AC:

AN:

39382

South Asian (SAS)

AF:

0.0518

AC:

4343

AN:

83796

European-Finnish (FIN)

AF:

0.00610

AC:

316

AN:

51844

Middle Eastern (MID)

AF:

0.0524

AC:

291

AN:

5552

European-Non Finnish (NFE)

AF:

0.0125

AC:

13874

AN:

1108160

Other (OTH)

AF:

0.0181

AC:

1089

AN:

60032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

1198

2397

3595

4794

5992

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.0120

AC:

1827

AN:

152304

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

890

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00226

AC:

AN:

41566

American (AMR)

AF:

0.0143

AC:

219

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0320

AC:

111

AN:

3472

East Asian (EAS)

AF:

0.000579

AC:

AN:

5178

South Asian (SAS)

AF:

0.0524

AC:

253

AN:

4826

European-Finnish (FIN)

AF:

0.00612

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0152

AC:

1037

AN:

68014

Other (OTH)

AF:

0.0161

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

182

273

364

455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0128

Hom.:

Bravo

AF:

0.0112

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Nov 06, 2020

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 29, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital myasthenic syndrome

Benign:2

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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. -

Congenital myasthenic syndrome 4A

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

-0.24

PromoterAI

-0.20

Neutral

(source)

Mutation Taster

=299/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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