rs72835059

Variant names:

• chr17-4902094-G-A
• rs72835059
• NM_001145536.2:c.*1561G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145536.2(C17orf107):​c.*1561G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,613,774 control chromosomes in the GnomAD database, including 6,107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.072 (448 hom., cov: 32)
  • Exomes 𝑓: 0.085 (5659 hom.)
• Consequence: C17orf107 NM_001145536.2 3_prime_UTR
• Scores: Splicing: ADA: 0.02643
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.559
• Publications: 8 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-4902094-G-A is Benign according to our data. Variant chr17-4902094-G-A is described in ClinVar as Benign. ClinVar VariationId is 128765.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0917 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145536.2. 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
	C17orf107	NM_001145536.2	MANE Select	c.*1561G>A		3_prime_UTR	Exon 3 of 3	NP_001139008.1
	CHRNE	NM_000080.4	MANE Select	c.345-7C>T		splice_region intron	N/A	NP_000071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C17orf107	ENST00000381365.4	TSL:2 MANE Select	c.*1561G>A		3_prime_UTR	Exon 3 of 3	ENSP00000370770.3
	CHRNE	ENST00000649488.2	MANE Select	c.345-7C>T		splice_region intron	N/A	ENSP00000497829.1
	CHRNE	ENST00000649830.1		c.-589-7C>T		splice_region intron	N/A	ENSP00000496907.1

Frequencies

GnomAD3 genomes AF: 0.0724 AC: 10994 AN: 151950 Hom.: 447 Cov.: 32

Gnomad AFR AF: 0.0312

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.0601

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0494

Gnomad SAS AF: 0.0336

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0936

Gnomad OTH AF: 0.0584

GnomAD2 exomes AF: 0.0741 AC: 18597 AN: 250942 AF XY: 0.0743

Gnomad AFR exome AF: 0.0280

Gnomad AMR exome AF: 0.0471

Gnomad ASJ exome AF: 0.0602

Gnomad EAS exome AF: 0.0426

Gnomad FIN exome AF: 0.138

Gnomad NFE exome AF: 0.0949

Gnomad OTH exome AF: 0.0821

GnomAD4 exome AF: 0.0846 AC: 123724 AN: 1461702 Hom.: 5659 Cov.: 37 AF XY: 0.0833 AC XY: 60570 AN XY: 727138

African (AFR) AF: 0.0279 AC: 933 AN: 33480

American (AMR) AF: 0.0477 AC: 2133 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0592 AC: 1546 AN: 26136

East Asian (EAS) AF: 0.0698 AC: 2772 AN: 39698

South Asian (SAS) AF: 0.0292 AC: 2522 AN: 86252

European-Finnish (FIN) AF: 0.135 AC: 7213 AN: 53300

Middle Eastern (MID) AF: 0.0636 AC: 367 AN: 5768

European-Non Finnish (NFE) AF: 0.0915 AC: 101727 AN: 1111952

Other (OTH) AF: 0.0747 AC: 4511 AN: 60394

GnomAD4 genome AF: 0.0723 AC: 10993 AN: 152072 Hom.: 448 Cov.: 32 AF XY: 0.0739 AC XY: 5494 AN XY: 74350

African (AFR) AF: 0.0312 AC: 1295 AN: 41504

American (AMR) AF: 0.0601 AC: 918 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0648 AC: 225 AN: 3472

East Asian (EAS) AF: 0.0495 AC: 255 AN: 5150

South Asian (SAS) AF: 0.0336 AC: 162 AN: 4822

European-Finnish (FIN) AF: 0.144 AC: 1526 AN: 10568

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0936 AC: 6362 AN: 67952

Other (OTH) AF: 0.0573 AC: 121 AN: 2112

Alfa AF: 0.0787 Hom.: 385

Bravo AF: 0.0620

Asia WGS AF: 0.0390 AC: 136 AN: 3478

EpiCase AF: 0.0893

EpiControl AF: 0.0897

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Jul 29, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Jun 23, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Congenital myasthenic syndrome Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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.

Sep 16, 2020

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Congenital myasthenic syndrome 4A Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.2
DANN	Benign	0.93
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.026
dbscSNV1_RF	Benign	0.022
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs72835059; hg19: chr17-4805389; COSMIC: COSV53420793; COSMIC: COSV53420793;