rs200490160
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate
The NM_000744.7(CHRNA4):c.77-10C>T 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 0.00000311 in 1,609,956 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
CHRNA4
NM_000744.7 splice_polypyrimidine_tract, intron
NM_000744.7 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0001953
2
Clinical Significance
Conservation
PhyloP100: 0.471
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 20-63359709-G-A is Benign according to our data. Variant chr20-63359709-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 543549.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.77-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000370263.9 | |||
CHRNA4 | NM_001256573.2 | c.-470-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ||||
CHRNA4 | NR_046317.2 | n.261-10C>T | 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.77-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246536Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134166
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GnomAD4 exome AF: 0.00000274 AC: 4AN: 1457658Hom.: 0 Cov.: 37 AF XY: 0.00000276 AC XY: 2AN XY: 725152
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152298Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0AN XY: 74472
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at