rs56377005

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000080.4(CHRNE):c.966C>T(p.Cys322=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 1,603,594 control chromosomes in the GnomAD database, including 351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 31 hom., cov: 32)

Exomes 𝑓: 0.015 ( 320 hom. )

Consequence

CHRNE
NM_000080.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.240

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 17-4899534-G-A is Benign according to our data. Variant chr17-4899534-G-A is described in ClinVar as [Benign]. Clinvar id is 254904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.24 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNE	NM_000080.4 linkuse as main transcript	c.966C>T	p.Cys322=	synonymous_variant	9/12	ENST00000649488.2	NP_000071.1
C17orf107	NM_001145536.2 linkuse as main transcript			upstream_gene_variant		ENST00000381365.4	NP_001139008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649488.2 linkuse as main transcript	c.966C>T	p.Cys322=	synonymous_variant	9/12		NM_000080.4	ENSP00000497829	P1
C17orf107	ENST00000381365.4 linkuse as main transcript			upstream_gene_variant		2	NM_001145536.2	ENSP00000370770	A2

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1829

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0143

Gnomad ASJ

AF:

0.0320

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0522

Gnomad FIN

AF:

0.00612

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0152

Gnomad OTH

AF:

0.0172

GnomAD3 exomes

AF:

0.0173

AC:

4005

AN:

231336

Hom.:

AF XY:

0.0195

AC XY:

2434

AN XY:

124866

show subpopulations

Gnomad AFR exome

AF:

0.00193

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0392

Gnomad EAS exome

AF:

0.000230

Gnomad SAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.00583

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0148

AC:

21434

AN:

1451290

Hom.:

320

Cov.:

AF XY:

0.0162

AC XY:

11641

AN XY:

720620

show subpopulations

Gnomad4 AFR exome

AF:

0.00183

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.0389

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.0518

Gnomad4 FIN exome

AF:

0.00610

Gnomad4 NFE exome

AF:

0.0125

Gnomad4 OTH exome

AF:

0.0181

GnomAD4 genome

AF:

0.0120

AC:

1827

AN:

152304

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

890

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.0143

Gnomad4 ASJ

AF:

0.0320

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0524

Gnomad4 FIN

AF:

0.00612

Gnomad4 NFE

AF:

0.0152

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0117

Hom.:

Bravo

AF:

0.0112

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 06, 2020	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 01, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Congenital myasthenic syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -

Congenital myasthenic syndrome 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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