rs780673811
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PP3_StrongBP6
The NM_000747.3(CHRNB1):c.1063C>T(p.Pro355Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000211 in 1,614,000 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
CHRNB1
NM_000747.3 missense
NM_000747.3 missense
Scores
10
7
1
Clinical Significance
Conservation
PhyloP100: 6.78
Genes affected
CHRNB1 (HGNC:1961): (cholinergic receptor nicotinic beta 1 subunit) The muscle acetylcholine receptor is composed of five subunits: two alpha subunits and one beta, one gamma, and one delta subunit. This gene encodes the beta subunit of the acetylcholine receptor. The acetylcholine receptor changes conformation upon acetylcholine binding leading to the opening of an ion-conducting channel across the plasma membrane. Mutations in this gene are associated with slow-channel congenital myasthenic syndrome. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.963
BP6
?
Variant 17-7455302-C-T is Benign according to our data. Variant chr17-7455302-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 576409.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB1 | NM_000747.3 | c.1063C>T | p.Pro355Ser | missense_variant | 9/11 | ENST00000306071.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB1 | ENST00000306071.7 | c.1063C>T | p.Pro355Ser | missense_variant | 9/11 | 1 | NM_000747.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 30
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GnomAD3 exomes AF: 0.0000676 AC: 17AN: 251474Hom.: 0 AF XY: 0.0000441 AC XY: 6AN XY: 135912
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GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727224
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3AN XY: 74332
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 24, 2023 | - - |
Congenital myasthenic syndrome 2A Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Pathogenic
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;.
REVEL
Pathogenic
Sift
Pathogenic
D;D;.
Sift4G
Pathogenic
D;D;D
Polyphen
D;.;.
Vest4
MutPred
Loss of helix (P = 0.0167);.;.;
MVP
MPC
ClinPred
D
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