rs45440192
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000744.7(CHRNA4):c.1759-14G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00338 in 1,612,144 control chromosomes in the GnomAD database, including 172 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.018 ( 84 hom., cov: 33)
Exomes 𝑓: 0.0019 ( 88 hom. )
Consequence
CHRNA4
NM_000744.7 splice_polypyrimidine_tract, intron
NM_000744.7 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.101
Genes affected
CHRNA4 (HGNC:1958): (cholinergic receptor nicotinic alpha 4 subunit) This gene encodes a nicotinic acetylcholine receptor, which belongs to a superfamily of ligand-gated ion channels that play a role in fast signal transmission at synapses. These pentameric receptors can bind acetylcholine, which causes an extensive change in conformation that leads to the opening of an ion-conducting channel across the plasma membrane. This protein is an integral membrane receptor subunit that can interact with either nAChR beta-2 or nAChR beta-4 to form a functional receptor. Mutations in this gene cause nocturnal frontal lobe epilepsy type 1. Polymorphisms in this gene that provide protection against nicotine addiction have been described. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
Variant 20-63346877-C-T is Benign according to our data. Variant chr20-63346877-C-T is described in ClinVar as [Benign]. Clinvar id is 136764.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-63346877-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.1759-14G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000370263.9 | |||
CHRNA4 | NM_001256573.2 | c.1231-14G>A | splice_polypyrimidine_tract_variant, intron_variant | ||||
CHRNA4 | NR_046317.2 | n.1968-14G>A | splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.1759-14G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0178 AC: 2704AN: 152216Hom.: 84 Cov.: 33
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GnomAD3 exomes AF: 0.00479 AC: 1183AN: 246988Hom.: 36 AF XY: 0.00346 AC XY: 465AN XY: 134262
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GnomAD4 exome AF: 0.00187 AC: 2737AN: 1459810Hom.: 88 Cov.: 32 AF XY: 0.00159 AC XY: 1154AN XY: 726254
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GnomAD4 genome ? AF: 0.0178 AC: 2706AN: 152334Hom.: 84 Cov.: 33 AF XY: 0.0172 AC XY: 1282AN XY: 74492
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 09, 2012 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at