15-78601997-G-A
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000743.5(CHRNA3):c.645C>T(p.Tyr215=) variant causes a synonymous change. The variant allele was found at a frequency of 0.305 in 1,613,104 control chromosomes in the GnomAD database, including 80,492 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.26 ( 6058 hom., cov: 31)
Exomes 𝑓: 0.31 ( 74434 hom. )
Consequence
CHRNA3
NM_000743.5 synonymous
NM_000743.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 5.50
Genes affected
CHRNA3 (HGNC:1957): (cholinergic receptor nicotinic alpha 3 subunit) This locus encodes a member of the nicotinic acetylcholine receptor family of proteins. Members of this family of proteins form pentameric complexes comprised of both alpha and beta subunits. This locus encodes an alpha-type subunit, as it contains characteristic adjacent cysteine residues. The encoded protein is a ligand-gated ion channel that likely plays a role in neurotransmission. Polymorphisms in this gene have been associated with an increased risk of smoking initiation and an increased susceptibility to lung cancer. Alternatively spliced transcript variants have been described. [provided by RefSeq, Nov 2009]
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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=-0.48).
BP6
?
Variant 15-78601997-G-A is Benign according to our data. Variant chr15-78601997-G-A is described in ClinVar as [Benign]. Clinvar id is 17503.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA3 | NM_000743.5 | c.645C>T | p.Tyr215= | synonymous_variant | 5/6 | ENST00000326828.6 | |
CHRNA3 | NM_001166694.2 | c.645C>T | p.Tyr215= | synonymous_variant | 5/6 | ||
CHRNA3 | XM_006720382.4 | c.444C>T | p.Tyr148= | synonymous_variant | 5/6 | ||
CHRNA3 | NR_046313.2 | n.847C>T | non_coding_transcript_exon_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA3 | ENST00000326828.6 | c.645C>T | p.Tyr215= | synonymous_variant | 5/6 | 1 | NM_000743.5 | P1 | |
CHRNA3 | ENST00000348639.7 | c.645C>T | p.Tyr215= | synonymous_variant | 5/6 | 1 | |||
CHRNA3 | ENST00000558903.1 | n.352C>T | non_coding_transcript_exon_variant | 2/2 | 4 | ||||
CHRNA3 | ENST00000559658.5 | c.645C>T | p.Tyr215= | synonymous_variant, NMD_transcript_variant | 5/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.258 AC: 39177AN: 151744Hom.: 6060 Cov.: 31
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GnomAD3 exomes AF: 0.269 AC: 67652AN: 251254Hom.: 10777 AF XY: 0.279 AC XY: 37940AN XY: 135766
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GnomAD4 exome AF: 0.310 AC: 453238AN: 1461244Hom.: 74434 Cov.: 42 AF XY: 0.310 AC XY: 225164AN XY: 726806
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GnomAD4 genome ? AF: 0.258 AC: 39187AN: 151860Hom.: 6058 Cov.: 31 AF XY: 0.254 AC XY: 18879AN XY: 74220
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ClinVar
Significance: Benign
Submissions summary: Benign:1Other:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Lung cancer susceptibility 2 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 01, 2008 | - - |
Smoking as a quantitative trait locus 3 Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 01, 2008 | - - |
Computational scores
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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