NM_000744.7(CHRNA4):c.1030dup (p.Val344fs) AND Autosomal dominant nocturnal frontal lobe epilepsy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 26, 2020
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001321398.5

Allele description [Variation Report for NM_000744.7(CHRNA4):c.1030dup (p.Val344fs)]

NM_000744.7(CHRNA4):c.1030dup (p.Val344fs)

Gene:

CHRNA4:cholinergic receptor nicotinic alpha 4 subunit [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_000744.7(CHRNA4):c.1030dup (p.Val344fs)

HGVS:

NC_000020.11:g.63350383dup
NG_011931.1:g.15963dup
NM_000744.7:c.1030dupMANE SELECT
NM_001256573.2:c.502dup
NP_000735.1:p.Val344fs
NP_001243502.1:p.Val168fs
NC_000020.10:g.61981732_61981733insC
NC_000020.10:g.61981735dup
NR_046317.2:n.1239dup

Protein change:

V168fs

Links:

dbSNP: rs1299258914

NCBI 1000 Genomes Browser:

rs1299258914

Molecular consequence:

NM_000744.7:c.1030dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256573.2:c.502dup - frameshift variant - [Sequence Ontology: SO:0001589]
NR_046317.2:n.1239dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE)
Identifiers:: MONDO: MONDO:0020300; MedGen: C3696898

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001512225	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 26, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001512225

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 26, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001512225.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CHRNA4 cause disease. This variant has not been reported in the literature in individuals with CHRNA4-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val344Glyfs*34) in the CHRNA4 gene. It is expected to result in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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