chr18-63318367-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_000633.3(BCL2):c.300C>T(p.Ala100=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,604,426 control chromosomes in the GnomAD database, including 222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.020 ( 36 hom., cov: 32)
Exomes 𝑓: 0.015 ( 186 hom. )
Consequence
BCL2
NM_000633.3 synonymous
NM_000633.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.46
Genes affected
BCL2 (HGNC:990): (BCL2 apoptosis regulator) This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. Constitutive expression of BCL2, such as in the case of translocation of BCL2 to Ig heavy chain locus, is thought to be the cause of follicular lymphoma. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
Variant 18-63318367-G-A is Benign according to our data. Variant chr18-63318367-G-A is described in ClinVar as [Benign]. Clinvar id is 3041306.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-1.46 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0201 (3057/152254) while in subpopulation AFR AF= 0.0355 (1477/41562). AF 95% confidence interval is 0.034. There are 36 homozygotes in gnomad4. There are 1399 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 3063 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BCL2 | NM_000633.3 | c.300C>T | p.Ala100= | synonymous_variant | 2/3 | ENST00000333681.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BCL2 | ENST00000333681.5 | c.300C>T | p.Ala100= | synonymous_variant | 2/3 | 1 | NM_000633.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0201 AC: 3063AN: 152138Hom.: 36 Cov.: 32
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GnomAD3 exomes AF: 0.0147 AC: 3475AN: 236506Hom.: 37 AF XY: 0.0142 AC XY: 1825AN XY: 128454
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GnomAD4 exome AF: 0.0145 AC: 21061AN: 1452172Hom.: 186 Cov.: 34 AF XY: 0.0143 AC XY: 10348AN XY: 721414
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
BCL2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 22, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at