dbSNP rs61733416: BCL2:p.Ala100Ala (chr18-63318367-G-A) – ACMG Classification: Benign (-14 pts)

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

Scores

Clinical Significance

Benign no assertion criteria provided 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]

BCL2 links:

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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 rank	MANE	Protein	UniProt
BCL2	NM_000633.3 link	c.300C>T	p.Ala100Ala	synonymous_variant	Exon 2 of 3	ENST00000333681.5	NP_000624.2	P10415-1A0A024R2B3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2	ENST00000333681.5 link	c.300C>T	p.Ala100Ala	synonymous_variant	Exon 2 of 3	1	NM_000633.3	ENSP00000329623.3		P10415-1

Frequencies

GnomAD3 genomes

AF:

0.0201

AC:

3063

AN:

152138

Hom.:

Cov.:

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.:

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.:

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

AF:

0.0201

AC:

3057

AN:

152254

Hom.:

Cov.:

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.:

Bravo

AF:

0.0213

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BCL2-related disorder

Benign:1

Feb 22, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over