20-63356000-G-T
Variant names:
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7
The NM_000744.7(CHRNA4):c.358C>A(p.Arg120Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000661 in 151,178 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: 30)
Consequence
CHRNA4
NM_000744.7 synonymous
NM_000744.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.550
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 -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
Variant 20-63356000-G-T is Benign according to our data. Variant chr20-63356000-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1621487.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.55 with no splicing effect.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CHRNA4 | NM_000744.7 | c.358C>A | p.Arg120Arg | synonymous_variant | Exon 4 of 6 | ENST00000370263.9 | NP_000735.1 | |
| CHRNA4 | NM_001256573.2 | c.-189C>A | 5_prime_UTR_variant | Exon 4 of 6 | NP_001243502.1 | |||
| CHRNA4 | NR_046317.2 | n.567C>A | non_coding_transcript_exon_variant | Exon 4 of 6 |
Ensembl
Frequencies
GnomAD3 genomes 0.00000661 AC: 1AN: 151178Hom.: 0 Cov.: 30
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GnomAD4 exome Cov.: 33
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GnomAD4 genome 0.00000661 AC: 1AN: 151178Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 73772
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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
Feb 12, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at