chr17-4898793-G-A

Position:

chr17-4898793-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000080.4(CHRNE):c.1425C>T(p.Leu475=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000336 in 1,608,098 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

CHRNE
NM_000080.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.08

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-4898793-G-A is Benign according to our data. Variant chr17-4898793-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 254893.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.08 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00183 (279/152326) while in subpopulation AFR AF= 0.00647 (269/41576). AF 95% confidence interval is 0.00584. There are 3 homozygotes in gnomad4. There are 128 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHRNE	NM_000080.4 linkuse as main transcript	c.1425C>T	p.Leu475=	synonymous_variant	12/12	ENST00000649488.2
CHRNE	XM_017024115.2 linkuse as main transcript	c.1389C>T	p.Leu463=	synonymous_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CHRNE	ENST00000649488.2 linkuse as main transcript	c.1425C>T	p.Leu475=	synonymous_variant	12/12		NM_000080.4	P1
CHRNE	ENST00000649830.1 linkuse as main transcript	c.*61C>T		3_prime_UTR_variant	11/11
CHRNE	ENST00000572438.1 linkuse as main transcript	n.1111C>T		non_coding_transcript_exon_variant	7/7	5
CHRNE	ENST00000652550.1 linkuse as main transcript	n.1151C>T		non_coding_transcript_exon_variant	4/4

Frequencies

GnomAD3 genomes

AF:

0.00183

AC:

279

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00649

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000418

AC:

AN:

236676

Hom.:

AF XY:

0.000289

AC XY:

AN XY:

127992

show subpopulations

Gnomad AFR exome

AF:

0.00612

Gnomad AMR exome

AF:

0.000152

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000693

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000936

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000180

AC:

262

AN:

1455772

Hom.:

Cov.:

AF XY:

0.000142

AC XY:

103

AN XY:

723480

show subpopulations

Gnomad4 AFR exome

AF:

0.00610

Gnomad4 AMR exome

AF:

0.000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000942

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.000332

GnomAD4 genome

AF:

0.00183

AC:

279

AN:

152326

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.00647

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000933

Hom.:

Bravo

AF:

0.00218

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Dec 22, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Congenital myasthenic syndrome

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Natera, Inc.	Oct 24, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -

Congenital myasthenic syndrome 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.9

DANN

Benign

0.91

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

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