rs112051150
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2
The NM_000744.7(CHRNA4):c.180C>T(p.Asp60=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000144 in 1,460,378 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: not found (cov: 34)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
CHRNA4
NM_000744.7 synonymous
NM_000744.7 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.618
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 -9 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.46).
BP6
?
Variant 20-63359596-G-A is Benign according to our data. Variant chr20-63359596-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2038859.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.618 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.180C>T | p.Asp60= | synonymous_variant | 2/6 | ENST00000370263.9 | |
CHRNA4 | NM_001256573.2 | c.-367C>T | 5_prime_UTR_variant | 2/6 | |||
CHRNA4 | NR_046317.2 | n.364C>T | non_coding_transcript_exon_variant | 2/6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.180C>T | p.Asp60= | synonymous_variant | 2/6 | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 34
GnomAD3 genomes
?
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34
GnomAD3 exomes AF: 0.00000800 AC: 2AN: 249850Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135648
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GnomAD4 exome AF: 0.0000144 AC: 21AN: 1460378Hom.: 0 Cov.: 37 AF XY: 0.0000138 AC XY: 10AN XY: 726482
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GnomAD4 genome ? Cov.: 34
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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 | Jun 22, 2022 | - - |
Computational scores
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Name
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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