rs55806270

Positions:

• chr17-4898730-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000080.4(CHRNE):​c.*6A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00689 in 1,608,722 control chromosomes in the GnomAD database, including 50 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0046 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0071 (48 hom.)
• Consequence: CHRNE NM_000080.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.241

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 17-4898730-T-C is Benign according to our data. Variant chr17-4898730-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 193972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-4898730-T-C is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00459 (699/152190) while in subpopulation NFE AF= 0.00859 (584/67976). AF 95% confidence interval is 0.00801. There are 2 homozygotes in gnomad4. There are 267 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRNE	NM_000080.4	c.*6A>G		3_prime_UTR_variant	12/12	ENST00000649488.2	NP_000071.1
CHRNE	XM_017024115.2	c.*6A>G		3_prime_UTR_variant	13/13		XP_016879604.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRNE	ENST00000649488.2	c.*6A>G		3_prime_UTR_variant	12/12		NM_000080.4	ENSP00000497829	P1
CHRNE	ENST00000649830.1	c.*124A>G		3_prime_UTR_variant	11/11			ENSP00000496907
CHRNE	ENST00000572438.1	n.1174A>G		non_coding_transcript_exon_variant	7/7	5
CHRNE	ENST00000652550.1	n.1214A>G		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.00460 AC: 699 AN: 152072 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.00147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000525

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00226

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00859

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00415 AC: 999 AN: 240770 Hom.: 2 AF XY: 0.00410 AC XY: 534 AN XY: 130202

Gnomad AFR exome AF: 0.00131

Gnomad AMR exome AF: 0.000747

Gnomad ASJ exome AF: 0.00185

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000954

Gnomad FIN exome AF: 0.00302

Gnomad NFE exome AF: 0.00755

Gnomad OTH exome AF: 0.00429

GnomAD4 exome AF: 0.00713 AC: 10391 AN: 1456532 Hom.: 48 Cov.: 34 AF XY: 0.00702 AC XY: 5086 AN XY: 724014

Gnomad4 AFR exome AF: 0.000837

Gnomad4 AMR exome AF: 0.000843

Gnomad4 ASJ exome AF: 0.00247

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000964

Gnomad4 FIN exome AF: 0.00438

Gnomad4 NFE exome AF: 0.00862

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.00459 AC: 699 AN: 152190 Hom.: 2 Cov.: 33 AF XY: 0.00359 AC XY: 267 AN XY: 74418

Gnomad4 AFR AF: 0.00147

Gnomad4 AMR AF: 0.000524

Gnomad4 ASJ AF: 0.00375

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00226

Gnomad4 NFE AF: 0.00859

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00679 Hom.: 1

Bravo AF: 0.00417

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Nov 13, 2017	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 15, 2015	- -

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	CHRNE: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital myasthenic syndrome Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs55806270; hg19: chr17-4802025;