rs4790235

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.53G>T(p.Gly18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0314 in 1,614,008 control chromosomes in the GnomAD database, including 2,014 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G18S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.032 ( 200 hom., cov: 32)

Exomes 𝑓: 0.031 ( 1814 hom. )

Consequence

CHRNE
NM_000080.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.570

Publications

17 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014411211).

BP6

Variant 17-4902757-C-A is Benign according to our data. Variant chr17-4902757-C-A is described in ClinVar as Benign. ClinVar VariationId is 128768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000080.4. 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
	CHRNE	NM_000080.4	MANE Select	c.53G>T	p.Gly18Val	missense	Exon 2 of 12	NP_000071.1	Q04844
	C17orf107	NM_001145536.2	MANE Select	c.*2224C>A		3_prime_UTR	Exon 3 of 3	NP_001139008.1	Q6ZR85

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRNE	ENST00000649488.2	MANE Select	c.53G>T	p.Gly18Val	missense	Exon 2 of 12	ENSP00000497829.1	Q04844
C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*2224C>A		3_prime_UTR	Exon 3 of 3	ENSP00000370770.3	Q6ZR85
CHRNE	ENST00000649830.1		c.-881G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 11	ENSP00000496907.1	A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.0319

AC:

4852

AN:

152026

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00824

Gnomad AMI

AF:

0.0749

Gnomad AMR

AF:

0.136

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0269

Gnomad OTH

AF:

0.0430

GnomAD2 exomes

AF:

0.0487

AC:

12243

AN:

251414

AF XY:

0.0412

show subpopulations

Gnomad AFR exome

AF:

0.00714

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0348

Gnomad NFE exome

AF:

0.0249

Gnomad OTH exome

AF:

0.0391

GnomAD4 exome

AF:

0.0313

AC:

45770

AN:

1461864

Hom.:

1814

Cov.:

AF XY:

0.0298

AC XY:

21684

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.00582

AC:

195

AN:

33480

American (AMR)

AF:

0.219

AC:

9781

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00536

AC:

140

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0114

AC:

982

AN:

86258

European-Finnish (FIN)

AF:

0.0339

AC:

1810

AN:

53412

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0280

AC:

31117

AN:

1111992

Other (OTH)

AF:

0.0279

AC:

1683

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

2904

5809

8713

11618

14522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1274

2548

3822

5096

6370

<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:

0.0319

AC:

4860

AN:

152144

Hom.:

200

Cov.:

AF XY:

0.0337

AC XY:

2510

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.00822

AC:

341

AN:

41506

American (AMR)

AF:

0.136

AC:

2078

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.000194

AC:

AN:

5158

South Asian (SAS)

AF:

0.00768

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0376

AC:

399

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0269

AC:

1827

AN:

67990

Other (OTH)

AF:

0.0426

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

222

443

665

886

1108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

184

230

<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:

0.0270

Hom.:

562

Bravo

AF:

0.0436

TwinsUK

AF:

0.0243

AC:

ALSPAC

AF:

0.0257

AC:

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.0223

AC:

192

ExAC

AF:

0.0406

AC:

4935

Asia WGS

AF:

0.0100

AC:

AN:

3478

EpiCase

AF:

0.0233

EpiControl

AF:

0.0262

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (5)

Congenital myasthenic syndrome (2)

not provided (2)

Congenital myasthenic syndrome 4A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.8

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.069

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

PhyloP100

-0.57

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.48

REVEL

Benign

0.13

Sift

Benign

0.56

Sift4G

Benign

0.55

Polyphen

0.084

Vest4

0.11

MPC

0.75

ClinPred

0.015

GERP RS

1.8

PromoterAI

-0.021

Neutral

(source)

Varity_R

0.041

gMVP

0.34

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over