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GeneBe

18-63318367-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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.46
Variant links:
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 -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.69).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
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
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-1.46 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
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
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 3063 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
BCL2NM_000633.3 linkuse as main transcriptc.300C>T p.Ala100= synonymous_variant 2/3 ENST00000333681.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
BCL2ENST00000333681.5 linkuse as main transcriptc.300C>T p.Ala100= synonymous_variant 2/31 NM_000633.3 P1P10415-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0201
AC:
3063
AN:
152138
Hom.:
36
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0356
Gnomad AMI
AF:
0.0154
Gnomad AMR
AF:
0.0122
Gnomad ASJ
AF:
0.00403
Gnomad EAS
AF:
0.0304
Gnomad SAS
AF:
0.00973
Gnomad FIN
AF:
0.00659
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.0154
Gnomad OTH
AF:
0.0215
GnomAD3 exomes
AF:
0.0147
AC:
3475
AN:
236506
Hom.:
37
AF XY:
0.0142
AC XY:
1825
AN XY:
128454
show subpopulations
Gnomad AFR exome
AF:
0.0354
Gnomad AMR exome
AF:
0.00993
Gnomad ASJ exome
AF:
0.00396
Gnomad EAS exome
AF:
0.0326
Gnomad SAS exome
AF:
0.00891
Gnomad FIN exome
AF:
0.00660
Gnomad NFE exome
AF:
0.0143
Gnomad OTH exome
AF:
0.0139
GnomAD4 exome
AF:
0.0145
AC:
21061
AN:
1452172
Hom.:
186
Cov.:
34
AF XY:
0.0143
AC XY:
10348
AN XY:
721414
show subpopulations
Gnomad4 AFR exome
AF:
0.0348
Gnomad4 AMR exome
AF:
0.0108
Gnomad4 ASJ exome
AF:
0.00377
Gnomad4 EAS exome
AF:
0.0232
Gnomad4 SAS exome
AF:
0.00817
Gnomad4 FIN exome
AF:
0.00727
Gnomad4 NFE exome
AF:
0.0147
Gnomad4 OTH exome
AF:
0.0171
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0201
AC:
3057
AN:
152254
Hom.:
36
Cov.:
32
AF XY:
0.0188
AC XY:
1399
AN XY:
74430
show subpopulations
Gnomad4 AFR
AF:
0.0355
Gnomad4 AMR
AF:
0.0121
Gnomad4 ASJ
AF:
0.00403
Gnomad4 EAS
AF:
0.0302
Gnomad4 SAS
AF:
0.00933
Gnomad4 FIN
AF:
0.00659
Gnomad4 NFE
AF:
0.0154
Gnomad4 OTH
AF:
0.0213
Alfa
AF:
0.0180
Hom.:
9
Bravo
AF:
0.0213
Asia WGS
AF:
0.0210
AC:
73
AN:
3478

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 submitterclinical testingPreventionGenetics, part of Exact SciencesFeb 22, 2019This 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.69
Cadd
Benign
10
Dann
Benign
0.94

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs61733416; hg19: chr18-60985600; API