dbSNP rs188564977: CHRNE:c.1220-5G>T (chr17-4899112-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_000080.4(CHRNE):c.1220-5G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000962 in 1,454,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

CHRNE
NM_000080.4 splice_region, intron

Scores

Splicing: ADA: 0.00001703

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53

Publications

0 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 -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-4899112-C-A is Benign according to our data. Variant chr17-4899112-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2817918.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHRNE	NM_000080.4	MANE Select	c.1220-5G>T		splice_region intron	N/A	NP_000071.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHRNE	ENST00000649488.2	MANE Select	c.1220-5G>T	splice_region intron	N/A	ENSP00000497829.1
CHRNE	ENST00000649830.1		c.287-5G>T	splice_region intron	N/A	ENSP00000496907.1
CHRNE	ENST00000572438.1	TSL:5	n.906-5G>T	splice_region intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000437

AC:

AN:

228696

AF XY:

0.00000795

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000984

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000962

AC:

AN:

1454596

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

723252

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.00

AC:

AN:

44150

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

39572

South Asian (SAS)

AF:

0.00

AC:

AN:

85388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1110080

Other (OTH)

AF:

0.00

AC:

AN:

60094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.561

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 4A

Benign:1

Dec 02, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.45

(source)

DANN

Benign

0.86

PhyloP100

-1.5

PromoterAI

-0.00080

Neutral

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000017

dbscSNV1_RF

Benign

0.0

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over