Genetic Variant CHRNE:c.1033-3_1033-2insTGCCCCTGCCCC (chr17-4899386-T-TGGGGCAGGGGCA) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000080.4(CHRNE):c.1033-3_1033-2insTGCCCCTGCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000289 in 1,381,788 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

CHRNE
NM_000080.4 splice_region, intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0980

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 links:

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

C17orf107 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 17-4899386-T-TGGGGCAGGGGCA is Benign according to our data. Variant chr17-4899386-T-TGGGGCAGGGGCA is described in ClinVar as Likely_benign. ClinVar VariationId is 1594365.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.1033-3_1033-2insTGCCCCTGCCCC		splice_region intron	N/A	NP_000071.1
	C17orf107	NM_001145536.2	MANE Select	c.-377_-376insGGGGCAGGGGCA		upstream_gene	N/A	NP_001139008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CHRNE	ENST00000649488.2	MANE Select	c.1033-3_1033-2insTGCCCCTGCCCC	splice_region intron	N/A	ENSP00000497829.1
CHRNE	ENST00000649830.1		c.100-3_100-2insTGCCCCTGCCCC	splice_region intron	N/A	ENSP00000496907.1
CHRNE	ENST00000572438.1	TSL:5	n.719-3_719-2insTGCCCCTGCCCC	splice_region intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

132540

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000289

AC:

AN:

1381788

Hom.:

Cov.:

AF XY:

0.00000440

AC XY:

AN XY:

681866

show subpopulations

African (AFR)

AF:

0.0000320

AC:

AN:

31250

American (AMR)

AF:

0.00

AC:

AN:

33698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24408

East Asian (EAS)

AF:

0.0000557

AC:

AN:

35886

South Asian (SAS)

AF:

0.00

AC:

AN:

78848

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39382

Middle Eastern (MID)

AF:

0.000212

AC:

AN:

4708

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076248

Other (OTH)

AF:

0.00

AC:

AN:

57360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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.:

Alfa

AF:

0.00

Hom.:

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 05, 2023

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

PhyloP100

0.098

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-4899386-TGGGGCA-TGGGGCAGGGGCAGGGGCA

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