Genetic Variant CHRNE:c.*6A>C (chr17-4898730-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000080.4(CHRNE):c.*6A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,546 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CHRNE
NM_000080.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.241

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital myasthenic syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: Illumina
congenital myasthenic syndrome 4A
Inheritance: AD, AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4B
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia
congenital myasthenic syndrome 4C
Inheritance: AR Classification: STRONG Submitted by: Genomics England PanelApp
postsynaptic congenital myasthenic syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

CHRNE links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHRNE	NM_000080.4 link	c.*6A>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000649488.2	NP_000071.1
CHRNE	XM_017024115.2 link	c.*6A>C		3_prime_UTR_variant	Exon 13 of 13		XP_016879604.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
CHRNE	ENST00000649488.2 link	c.*6A>C	3_prime_UTR_variant	Exon 12 of 12		NM_000080.4	ENSP00000497829.1
CHRNE	ENST00000572438.1 link	n.1174A>C	non_coding_transcript_exon_variant	Exon 7 of 7	5
CHRNE	ENST00000652550.1 link	n.1214A>C	non_coding_transcript_exon_variant	Exon 4 of 4
CHRNE	ENST00000649830.1 link	c.*124A>C	3_prime_UTR_variant	Exon 11 of 11			ENSP00000496907.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456546

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724020

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33454

American (AMR)

AF:

0.00

AC:

AN:

43880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25912

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.00

AC:

AN:

85100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52750

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1109932

Other (OTH)

AF:

0.0000166

AC:

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.27

(source)

DANN

Benign

0.43

PhyloP100

-0.24

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over