rs796052329
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PM4_SupportingBS1_SupportingBS2
The NM_000748.3(CHRNB2):c.363_365del(p.Asn122del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000487 in 1,600,848 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. Y120Y) has been classified as Likely benign.
Frequency
Consequence
NM_000748.3 inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CHRNB2 | NM_000748.3 | c.363_365del | p.Asn122del | inframe_deletion | 4/6 | ENST00000368476.4 | |
CHRNB2 | XM_017000180.3 | c.-12_-10del | 5_prime_UTR_variant | 1/3 | |||
CHRNB2 | XR_001736952.3 | n.630_632del | non_coding_transcript_exon_variant | 4/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CHRNB2 | ENST00000368476.4 | c.363_365del | p.Asn122del | inframe_deletion | 4/6 | 1 | NM_000748.3 | P4 | |
CHRNB2 | ENST00000637900.1 | c.369_371del | p.Asn124del | inframe_deletion | 4/6 | 5 | A1 | ||
CHRNB2 | ENST00000636034.1 | c.363_365del | p.Asn122del | inframe_deletion, NMD_transcript_variant | 4/9 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000290 AC: 44AN: 151980Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000532 AC: 13AN: 244296Hom.: 0 AF XY: 0.0000304 AC XY: 4AN XY: 131782
GnomAD4 exome AF: 0.0000235 AC: 34AN: 1448750Hom.: 0 AF XY: 0.0000125 AC XY: 9AN XY: 720856
GnomAD4 genome ? AF: 0.000289 AC: 44AN: 152098Hom.: 0 Cov.: 31 AF XY: 0.000269 AC XY: 20AN XY: 74350
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 25, 2023 | In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Dec 29, 2017 | - - |
Autosomal dominant nocturnal frontal lobe epilepsy 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | New York Genome Center | Jan 21, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 06, 2017 | The c.363_365delCAA variant (also known as p.N122del) is located in coding exon 4 of the CHRNB2 gene. This variant results from an in-frame CAA deletion at nucleotide positions 363 to 365. This results in the in-frame deletion of an asparagine at codon 122. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by PROVEAN in silico analysis (Choi Y et al., PLoS ONE 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. - |
Autosomal dominant nocturnal frontal lobe epilepsy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at