rs148340961

chr17-4899175-CGGGCCA-Cchr17-4899175-CGGGCCA-CGGGCCAGGGCCA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000080.4(CHRNE):c.1219+17_1219+22del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 1,594,800 control chromosomes in the GnomAD database, including 5,697 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.071 (434 hom., cov: 31)
  • Exomes 𝑓: 0.083 (5263 hom.)
• Consequence: CHRNE NM_000080.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.355

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 17-4899175-CGGGCCA-C is Benign according to our data. Variant chr17-4899175-CGGGCCA-C is described in ClinVar as [Benign]. Clinvar id is 254890.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-4899175-CGGGCCA-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNE	NM_000080.4	c.1219+17_1219+22del		intron_variant		ENST00000649488.2
CHRNE	XM_017024115.2	c.1183+17_1183+22del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNE	ENST00000649488.2	c.1219+17_1219+22del		intron_variant			NM_000080.4	P1
CHRNE	ENST00000649830.1	c.286+17_286+22del		intron_variant
CHRNE	ENST00000572438.1	n.905+17_905+22del		intron_variant, non_coding_transcript_variant		5
CHRNE	ENST00000652550.1	n.949+17_949+22del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10871 AN: 152056 Hom.: 433 Cov.: 31

Gnomad AFR AF: 0.0321

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0595

Gnomad ASJ AF: 0.0648

Gnomad EAS AF: 0.0482

Gnomad SAS AF: 0.0356

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0913

Gnomad OTH AF: 0.0564

GnomAD3 exomes AF: 0.0690 AC: 14452 AN: 209320 Hom.: 567 AF XY: 0.0692 AC XY: 7999 AN XY: 115672

Gnomad AFR exome AF: 0.0268

Gnomad AMR exome AF: 0.0457

Gnomad ASJ exome AF: 0.0583

Gnomad EAS exome AF: 0.0405

Gnomad SAS exome AF: 0.0287

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.0901

Gnomad OTH exome AF: 0.0766

GnomAD4 exome AF: 0.0828 AC: 119405 AN: 1442626 Hom.: 5263 AF XY: 0.0814 AC XY: 58365 AN XY: 716716

Gnomad4 AFR exome AF: 0.0285

Gnomad4 AMR exome AF: 0.0468

Gnomad4 ASJ exome AF: 0.0594

Gnomad4 EAS exome AF: 0.0704

Gnomad4 SAS exome AF: 0.0289

Gnomad4 FIN exome AF: 0.133

Gnomad4 NFE exome AF: 0.0894

Gnomad4 OTH exome AF: 0.0729

GnomAD4 genome AF: 0.0714 AC: 10872 AN: 152174 Hom.: 434 Cov.: 31 AF XY: 0.0732 AC XY: 5443 AN XY: 74398

Gnomad4 AFR AF: 0.0321

Gnomad4 AMR AF: 0.0594

Gnomad4 ASJ AF: 0.0648

Gnomad4 EAS AF: 0.0483

Gnomad4 SAS AF: 0.0356

Gnomad4 FIN AF: 0.144

Gnomad4 NFE AF: 0.0913

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0790 Hom.: 84

Bravo AF: 0.0615

Asia WGS AF: 0.0390 AC: 136 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Nov 16, 2015	- -

Congenital myasthenic syndrome 4A Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 29, 2018

- -

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: rs148340961; hg19: chr17-4802470;