Variant rs748144899 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BP4

The ENST00000649830.1(CHRNE):c.-887-396C>T variant causes a intron change. The variant allele was found at a frequency of 0.0000263 in 1,214,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

CHRNE
ENST00000649830.1 intron

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:4U:1

Conservation

PhyloP100: 4.35

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:):

C17orf107 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5

Variant 17-4903159-G-A is Pathogenic according to our data. Variant chr17-4903159-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 18353.We mark this variant Likely_pathogenic, oryginal submissions are: {Uncertain_significance=1, Likely_pathogenic=3}. Variant chr17-4903159-G-A is described in Lovd as [Pathogenic]. Variant chr17-4903159-G-A is described in Lovd as [Likely_pathogenic].

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein
CHRNE	XM_017024115.2 linkuse as main transcript	c.11-396C>T	intron_variant	XP_016879604.1
C17orf107	XR_007065253.1 linkuse as main transcript	n.2388+1038G>A	intron_variant
C17orf107	XR_007065254.1 linkuse as main transcript	n.2388+1038G>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649830.1 linkuse as main transcript	c.-887-396C>T		intron_variant				ENSP00000496907.1		A0A3B3IRM1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000292

AC:

AN:

1062806

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

541786

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000261

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000845

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000339

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:4Uncertain:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Congenital myasthenic syndrome 4A

Pathogenic:1Uncertain:1

Likely pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Jun 08, 2023	- -
Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 19, 2022	This variant occurs in a non-coding region of the CHRNE gene. It does not change the encoded amino acid sequence of the CHRNE protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with congenital myasthenic syndrome (PMID: 10211467). It has also been observed to segregate with disease in related individuals. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Congenital myasthenic syndrome 4C;C4225369:Congenital myasthenic syndrome 4B;C4225413:Congenital myasthenic syndrome 4A

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 08, 2022

- -

not provided

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2022

CHRNE: PM2, PM3, PP4, PS3:Supporting -

Congenital myasthenic syndrome 4C

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Apr 01, 1999

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.82

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over