rs2273502
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000744.7(CHRNA4):c.229-55G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0799 in 1,528,598 control chromosomes in the GnomAD database, including 5,730 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.096 ( 753 hom., cov: 31)
Exomes 𝑓: 0.078 ( 4977 hom. )
Consequence
CHRNA4
NM_000744.7 intron
NM_000744.7 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.892
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BP6
?
Variant 20-63356470-C-T is Benign according to our data. Variant chr20-63356470-C-T is described in ClinVar as [Benign]. Clinvar id is 1238055.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr20-63356470-C-T is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA4 | NM_000744.7 | c.229-55G>A | intron_variant | ENST00000370263.9 | |||
CHRNA4 | NM_001256573.2 | c.-318-55G>A | intron_variant | ||||
CHRNA4 | NR_046317.2 | n.413-55G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA4 | ENST00000370263.9 | c.229-55G>A | intron_variant | 1 | NM_000744.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0962 AC: 14600AN: 151792Hom.: 751 Cov.: 31
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GnomAD4 exome AF: 0.0781 AC: 107574AN: 1376688Hom.: 4977 Cov.: 24 AF XY: 0.0805 AC XY: 54932AN XY: 682258
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GnomAD4 genome ? AF: 0.0963 AC: 14625AN: 151910Hom.: 753 Cov.: 31 AF XY: 0.0972 AC XY: 7220AN XY: 74258
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 26, 2018 | - - |
Computational scores
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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