chr15-78601399-A-C
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS1
The NM_000743.5(CHRNA3):c.1243T>G(p.Phe415Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000429 in 1,614,012 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00042 ( 4 hom. )
Consequence
CHRNA3
NM_000743.5 missense
NM_000743.5 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 3.34
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0056548417).
BP6
?
Variant 15-78601399-A-C is Benign according to our data. Variant chr15-78601399-A-C is described in ClinVar as [Benign]. Clinvar id is 736331.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000423 (618/1461894) while in subpopulation AMR AF= 0.000894 (40/44724). AF 95% confidence interval is 0.000675. There are 4 homozygotes in gnomad4_exome. There are 292 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNA3 | NM_000743.5 | c.1243T>G | p.Phe415Val | missense_variant | 5/6 | ENST00000326828.6 | |
CHRNA3 | NM_001166694.2 | c.1243T>G | p.Phe415Val | missense_variant | 5/6 | ||
CHRNA3 | XM_006720382.4 | c.1042T>G | p.Phe348Val | missense_variant | 5/6 | ||
CHRNA3 | NR_046313.2 | n.1445T>G | non_coding_transcript_exon_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNA3 | ENST00000326828.6 | c.1243T>G | p.Phe415Val | missense_variant | 5/6 | 1 | NM_000743.5 | P1 | |
CHRNA3 | ENST00000348639.7 | c.1243T>G | p.Phe415Val | missense_variant | 5/6 | 1 | |||
CHRNA3 | ENST00000559658.5 | c.1243T>G | p.Phe415Val | missense_variant, NMD_transcript_variant | 5/8 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000493 AC: 75AN: 152118Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000871 AC: 219AN: 251442Hom.: 1 AF XY: 0.000905 AC XY: 123AN XY: 135898
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GnomAD4 exome AF: 0.000423 AC: 618AN: 1461894Hom.: 4 Cov.: 31 AF XY: 0.000402 AC XY: 292AN XY: 727248
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GnomAD4 genome ? AF: 0.000493 AC: 75AN: 152118Hom.: 0 Cov.: 31 AF XY: 0.000417 AC XY: 31AN XY: 74304
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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 13, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.33
ClinPred
T
GERP RS
Varity_R
gMVP
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