rs139171143

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_000080.4(CHRNE):c.1402G>T(p.Val468Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V468M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHRNE
NM_000080.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.492

Publications

11 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12414622).

BP6

Variant 17-4898816-C-A is Benign according to our data. Variant chr17-4898816-C-A is described in ClinVar as Benign. ClinVar VariationId is 2201526.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4 link	c.1402G>T	p.Val468Leu	missense_variant	Exon 12 of 12	ENST00000649488.2	NP_000071.1
CHRNE	XM_017024115.2 link	c.1366G>T	p.Val456Leu	missense_variant	Exon 13 of 13		XP_016879604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
CHRNE	ENST00000649488.2 link	c.1402G>T	p.Val468Leu	missense_variant	Exon 12 of 12		NM_000080.4	ENSP00000497829.1
CHRNE	ENST00000572438.1 link	n.1088G>T		non_coding_transcript_exon_variant	Exon 7 of 7	5
CHRNE	ENST00000652550.1 link	n.1128G>T		non_coding_transcript_exon_variant	Exon 4 of 4
CHRNE	ENST00000649830.1 link	c.*38G>T		3_prime_UTR_variant	Exon 11 of 11			ENSP00000496907.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1451196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720804

African (AFR)

AF:

0.00

AC:

AN:

33388

American (AMR)

AF:

0.00

AC:

AN:

42430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25844

East Asian (EAS)

AF:

0.00

AC:

AN:

39356

South Asian (SAS)

AF:

0.00

AC:

AN:

84318

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52304

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1107738

Other (OTH)

AF:

0.00

AC:

AN:

60064

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 4A

Benign:1

Oct 20, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.12

T;T

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.57

.;T

M_CAP

Benign

0.030

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-1.0

N;N

PhyloP100

-0.49

PrimateAI

Benign

0.44

PROVEAN

Benign

0.040

N;.

REVEL

Benign

0.20

Sift

Benign

0.44

T;.

Sift4G

Benign

0.78

T;.

Polyphen

0.0060

B;B

Vest4

0.026

MutPred

0.52

Loss of sheet (P = 0.0457);Loss of sheet (P = 0.0457);

MVP

0.74

MPC

0.17

ClinPred

0.11

GERP RS

0.89

Varity_R

0.084

gMVP

0.51

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over