rs61733416
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_000633.3(BCL2):c.300C>T(p.Ala100Ala) 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 (no stars).
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 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 no_assertion_criteria_provided, 0 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 GnomAd4 at 3057 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BCL2 | NM_000633.3 | c.300C>T | p.Ala100Ala | synonymous_variant | 2/3 | ENST00000333681.5 | NP_000624.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BCL2 | ENST00000333681.5 | c.300C>T | p.Ala100Ala | synonymous_variant | 2/3 | 1 | NM_000633.3 | ENSP00000329623.3 |
Frequencies
GnomAD3 genomes AF: 0.0201 AC: 3063AN: 152138Hom.: 36 Cov.: 32
GnomAD3 genomes
AF:
AC:
3063
AN:
152138
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: 0.0147 AC: 3475AN: 236506Hom.: 37 AF XY: 0.0142 AC XY: 1825AN XY: 128454
GnomAD3 exomes
AF:
AC:
3475
AN:
236506
Hom.:
AF XY:
AC XY:
1825
AN XY:
128454
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: 0.0145 AC: 21061AN: 1452172Hom.: 186 Cov.: 34 AF XY: 0.0143 AC XY: 10348AN XY: 721414
GnomAD4 exome
AF:
AC:
21061
AN:
1452172
Hom.:
Cov.:
34
AF XY:
AC XY:
10348
AN XY:
721414
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: 0.0201 AC: 3057AN: 152254Hom.: 36 Cov.: 32 AF XY: 0.0188 AC XY: 1399AN XY: 74430
GnomAD4 genome
AF:
AC:
3057
AN:
152254
Hom.:
Cov.:
32
AF XY:
AC XY:
1399
AN XY:
74430
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
73
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
BCL2-related disorder Benign:1
Benign, no assertion criteria provided | 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
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