rs12942540

Positions:

• chr17-4900778-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145536.2(C17orf107):​c.*245G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.142 in 1,608,764 control chromosomes in the GnomAD database, including 16,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.16 (2132 hom., cov: 33)
  • Exomes 𝑓: 0.14 (14757 hom.)
• Consequence: C17orf107 NM_001145536.2 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.232

Genes affected

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

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]

C17orf107 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 17-4900778-G-C is Benign according to our data. Variant chr17-4900778-G-C is described in ClinVar as [Benign]. Clinvar id is 254903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-4900778-G-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C17orf107	NM_001145536.2	c.*245G>C		3_prime_UTR_variant	3/3	ENST00000381365.4	NP_001139008.1
CHRNE	NM_000080.4	c.917+15C>G		intron_variant		ENST00000649488.2	NP_000071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C17orf107	ENST00000381365.4	c.*245G>C		3_prime_UTR_variant	3/3	2	NM_001145536.2	ENSP00000370770.3
CHRNE	ENST00000649488.2	c.917+15C>G		intron_variant			NM_000080.4	ENSP00000497829.1

Frequencies

GnomAD3 genomes AF: 0.161 AC: 24557 AN: 152162 Hom.: 2132 Cov.: 33

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0884

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.175

GnomAD3 exomes AF: 0.143 AC: 34080 AN: 238054 Hom.: 2493 AF XY: 0.143 AC XY: 18565 AN XY: 129902

Gnomad AFR exome AF: 0.214

Gnomad AMR exome AF: 0.158

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.0844

Gnomad SAS exome AF: 0.149

Gnomad FIN exome AF: 0.129

Gnomad NFE exome AF: 0.139

Gnomad OTH exome AF: 0.155

GnomAD4 exome AF: 0.140 AC: 204526 AN: 1456484 Hom.: 14757 Cov.: 32 AF XY: 0.141 AC XY: 101812 AN XY: 724428

Gnomad4 AFR exome AF: 0.216

Gnomad4 AMR exome AF: 0.161

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.137

Gnomad4 OTH exome AF: 0.145

GnomAD4 genome AF: 0.161 AC: 24575 AN: 152280 Hom.: 2132 Cov.: 33 AF XY: 0.160 AC XY: 11910 AN XY: 74454

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0886

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.172

Alfa AF: 0.146 Hom.: 326

Bravo AF: 0.169

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 04, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Congenital myasthenic syndrome 4A Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -

Congenital myasthenic syndrome 4C Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Congenital myasthenic syndrome 4B Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Congenital myasthenic syndrome Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs12942540; hg19: chr17-4804073; COSMIC: COSV53417534; COSMIC: COSV53417534;