rs1555546315

Positions:

• chr17-4899318-AGGCGGCCCGGGGGGCCTCGGGC-A
• chr17-4899318-AGGCGGCCCGGGGGGCCTCGGGC-AGGCGGCCCGGGGGGCCTCGGGCGGCGGCCCGGGGGGCCTCGGGC

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1 PM2

The NM_000080.4(CHRNE):​c.1077_1098del​(p.Pro360ArgfsTer18) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P359P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CHRNE NM_000080.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.93

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 Pathogenic. Variant got 10 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNE	NM_000080.4	c.1077_1098del	p.Pro360ArgfsTer18	frameshift_variant	10/12	ENST00000649488.2
CHRNE	XM_017024115.2	c.1041_1062del	p.Pro348ArgfsTer18	frameshift_variant	11/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNE	ENST00000649488.2	c.1077_1098del	p.Pro360ArgfsTer18	frameshift_variant	10/12		NM_000080.4	P1
CHRNE	ENST00000649830.1	c.144_165del	p.Pro49ArgfsTer18	frameshift_variant	10/11
CHRNE	ENST00000572438.1	n.763_784del		non_coding_transcript_exon_variant	5/7	5
CHRNE	ENST00000652550.1	n.807_828del		non_coding_transcript_exon_variant	2/4

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

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: rs1555546315; hg19: chr17-4802613;