chr15-32111781-G-A
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2
The NM_000746.6(CHRNA7):c.241-9G>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 0.000544 in 1,545,516 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0027 ( 4 hom., cov: 33)
Exomes 𝑓: 0.00031 ( 0 hom. )
Consequence
CHRNA7
NM_000746.6 splice_polypyrimidine_tract, intron
NM_000746.6 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0006264
2
Clinical Significance
Conservation
PhyloP100: -0.435
Genes affected
CHRNA7 (HGNC:1960): (cholinergic receptor nicotinic alpha 7 subunit) The nicotinic acetylcholine receptors (nAChRs) are members of a superfamily of ligand-gated ion channels that mediate fast signal transmission at synapses. The nAChRs are thought to be hetero-pentamers composed of homologous subunits. The proposed structure for each subunit is a conserved N-terminal extracellular domain followed by three conserved transmembrane domains, a variable cytoplasmic loop, a fourth conserved transmembrane domain, and a short C-terminal extracellular region. The protein encoded by this gene forms a homo-oligomeric channel, displays marked permeability to calcium ions and is a major component of brain nicotinic receptors that are blocked by, and highly sensitive to, alpha-bungarotoxin. Once this receptor binds acetylcholine, it undergoes an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane. This gene is located in a region identified as a major susceptibility locus for juvenile myoclonic epilepsy and a chromosomal location involved in the genetic transmission of schizophrenia. An evolutionarily recent partial duplication event in this region results in a hybrid containing sequence from this gene and a novel FAM7A gene. 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 -8 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.35).
BP6
Variant 15-32111781-G-A is Benign according to our data. Variant chr15-32111781-G-A is described in ClinVar as [Benign]. Clinvar id is 735528.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 408 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA7 | NM_000746.6 | c.241-9G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000306901.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA7 | ENST00000306901.9 | c.241-9G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000746.6 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00269 AC: 409AN: 152196Hom.: 4 Cov.: 33
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GnomAD3 exomes AF: 0.000638 AC: 159AN: 249224Hom.: 0 AF XY: 0.000513 AC XY: 69AN XY: 134518
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GnomAD4 exome AF: 0.000311 AC: 433AN: 1393202Hom.: 0 Cov.: 22 AF XY: 0.000291 AC XY: 203AN XY: 696584
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GnomAD4 genome AF: 0.00268 AC: 408AN: 152314Hom.: 4 Cov.: 33 AF XY: 0.00267 AC XY: 199AN XY: 74490
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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 | Invitae | Dec 31, 2019 | - - |
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