rs201514209
Positions:
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_000748.3(CHRNB2):c.772C>T(p.Leu258=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000245 in 1,614,246 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 4 hom. )
Consequence
CHRNB2
NM_000748.3 synonymous
NM_000748.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.771
Genes affected
CHRNB2 (HGNC:1962): (cholinergic receptor nicotinic beta 2 subunit) Neuronal acetylcholine receptors are homo- or heteropentameric complexes composed of homologous alpha and beta subunits. They belong to a superfamily of ligand-gated ion channels which allow the flow of sodium and potassium across the plasma membrane in response to ligands such as acetylcholine and nicotine. This gene encodes one of several beta subunits. Mutations in this gene are associated with autosomal dominant nocturnal frontal lobe epilepsy. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.44).
BP6
?
Variant 1-154571595-C-T is Benign according to our data. Variant chr1-154571595-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 477015.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.771 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000203 (31/152360) while in subpopulation SAS AF= 0.00621 (30/4832). AF 95% confidence interval is 0.00447. There are 0 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 31 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB2 | NM_000748.3 | c.772C>T | p.Leu258= | synonymous_variant | 5/6 | ENST00000368476.4 | |
CHRNB2 | XM_017000180.3 | c.262C>T | p.Leu88= | synonymous_variant | 2/3 | ||
CHRNB2 | XR_001736952.3 | n.1039C>T | non_coding_transcript_exon_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB2 | ENST00000368476.4 | c.772C>T | p.Leu258= | synonymous_variant | 5/6 | 1 | NM_000748.3 | P4 | |
CHRNB2 | ENST00000637900.1 | c.778C>T | p.Leu260= | synonymous_variant | 5/6 | 5 | A1 | ||
CHRNB2 | ENST00000636034.1 | c.772C>T | p.Leu258= | synonymous_variant, NMD_transcript_variant | 5/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000204 AC: 31AN: 152242Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
31
AN:
152242
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000640 AC: 161AN: 251474Hom.: 4 AF XY: 0.000758 AC XY: 103AN XY: 135912
GnomAD3 exomes
AF:
AC:
161
AN:
251474
Hom.:
AF XY:
AC XY:
103
AN XY:
135912
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000249 AC: 364AN: 1461886Hom.: 4 Cov.: 33 AF XY: 0.000333 AC XY: 242AN XY: 727246
GnomAD4 exome
AF:
AC:
364
AN:
1461886
Hom.:
Cov.:
33
AF XY:
AC XY:
242
AN XY:
727246
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000203 AC: 31AN: 152360Hom.: 0 Cov.: 32 AF XY: 0.000322 AC XY: 24AN XY: 74508
GnomAD4 genome
?
AF:
AC:
31
AN:
152360
Hom.:
Cov.:
32
AF XY:
AC XY:
24
AN XY:
74508
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
Asia WGS
AF:
AC:
7
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Autosomal dominant nocturnal frontal lobe epilepsy 3 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 12, 2021 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 15, 2023 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 22, 2016 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at