rs761361955

Positions:

• chr17-4899386-T-TGGGGCA
• chr17-4899386-T-TGGGGCAGGGGCA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000080.4(CHRNE):​c.1033-8_1033-3dupTGCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000329 in 1,533,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00023 (0 hom.)
• Consequence: CHRNE NM_000080.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0980

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 (HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP6: Variant 17-4899386-T-TGGGGCA is Benign according to our data. Variant chr17-4899386-T-TGGGGCA is described in ClinVar as [Likely_benign]. Clinvar id is 465850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNE	NM_000080.4	c.1033-8_1033-3dupTGCCCC		splice_region_variant, intron_variant		ENST00000649488.2	NP_000071.1
CHRNE	XM_017024115.2	c.997-8_997-3dupTGCCCC		splice_region_variant, intron_variant			XP_016879604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649488.2	c.1033-8_1033-3dupTGCCCC		splice_region_variant, intron_variant			NM_000080.4	ENSP00000497829.1

Frequencies

GnomAD3 genomes AF: 0.00122 AC: 186 AN: 151986 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00360

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000947

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000558 AC: 74 AN: 132540 Hom.: 0 AF XY: 0.000549 AC XY: 40 AN XY: 72816

Gnomad AFR exome AF: 0.00482

Gnomad AMR exome AF: 0.000577

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00217

Gnomad SAS exome AF: 0.000136

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000401

Gnomad OTH exome AF: 0.000257

GnomAD4 exome AF: 0.000232 AC: 320 AN: 1381788 Hom.: 0 Cov.: 35 AF XY: 0.000220 AC XY: 150 AN XY: 681866

Gnomad4 AFR exome AF: 0.00272

Gnomad4 AMR exome AF: 0.000356

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000864

Gnomad4 SAS exome AF: 0.000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000140

Gnomad4 OTH exome AF: 0.000506

GnomAD4 genome AF: 0.00122 AC: 185 AN: 152102 Hom.: 0 Cov.: 33 AF XY: 0.00117 AC XY: 87 AN XY: 74370

Gnomad4 AFR AF: 0.00356

Gnomad4 AMR AF: 0.000457

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000947

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000192 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 26, 2017

- -

Congenital myasthenic syndrome 4A Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

CHRNE-related disorder Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 12, 2024

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs761361955; hg19: chr17-4802681;