Variant rs2302315 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000649830.1(CHRNE):c.-887-370C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0898 in 1,511,588 control chromosomes in the GnomAD database, including 6,380 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 723 hom., cov: 31)

Exomes 𝑓: 0.089 ( 5657 hom. )

Consequence

CHRNE
ENST00000649830.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.756

Variant links:

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 links:

C17orf107 (HGNC:):

C17orf107 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 17-4903133-G-A is Benign according to our data. Variant chr17-4903133-G-A is described in ClinVar as [Benign]. Clinvar id is 254887.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
CHRNE	XM_017024115.2 linkuse as main transcript	c.11-370C>T	intron_variant
C17orf107	XR_007065253.1 linkuse as main transcript	n.2388+1012G>A	intron_variant, non_coding_transcript_variant
C17orf107	XR_007065254.1 linkuse as main transcript	n.2388+1012G>A	intron_variant, non_coding_transcript_variant
CHRNE	NM_000080.4 linkuse as main transcript		upstream_gene_variant	ENST00000649488.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHRNE	ENST00000649830.1 linkuse as main transcript	c.-887-370C>T		intron_variant
CHRNE	ENST00000649488.2 linkuse as main transcript			upstream_gene_variant			NM_000080.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0967

AC:

14706

AN:

152024

Hom.:

723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.116

Gnomad AMI

AF:

0.115

Gnomad AMR

AF:

0.0670

Gnomad ASJ

AF:

0.0677

Gnomad EAS

AF:

0.0497

Gnomad SAS

AF:

0.0356

Gnomad FIN

AF:

0.145

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0942

Gnomad OTH

AF:

0.0675

GnomAD4 exome

AF:

0.0890

AC:

120972

AN:

1359446

Hom.:

5657

AF XY:

0.0871

AC XY:

59278

AN XY:

680770

show subpopulations

Gnomad4 AFR exome

AF:

0.124

Gnomad4 AMR exome

AF:

0.0526

Gnomad4 ASJ exome

AF:

0.0610

Gnomad4 EAS exome

AF:

0.0728

Gnomad4 SAS exome

AF:

0.0307

Gnomad4 FIN exome

AF:

0.135

Gnomad4 NFE exome

AF:

0.0937

Gnomad4 OTH exome

AF:

0.0810

GnomAD4 genome

AF:

0.0967

AC:

14705

AN:

152142

Hom.:

723

Cov.:

AF XY:

0.0972

AC XY:

7231

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.116

Gnomad4 AMR

AF:

0.0669

Gnomad4 ASJ

AF:

0.0677

Gnomad4 EAS

AF:

0.0498

Gnomad4 SAS

AF:

0.0359

Gnomad4 FIN

AF:

0.145

Gnomad4 NFE

AF:

0.0942

Gnomad4 OTH

AF:

0.0663

Alfa

AF:

0.0964

Hom.:

Bravo

AF:

0.0901

Asia WGS

AF:

0.0440

AC:

153

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 28, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.87

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over