Variant 18-63318646-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000633.3(BCL2):c.21A>G(p.Thr7=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 1,612,024 control chromosomes in the GnomAD database, including 135,183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.32 ( 9647 hom., cov: 32)

Exomes 𝑓: 0.41 ( 125536 hom. )

Consequence

BCL2
NM_000633.3 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.699

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:

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=-0.7).

BP6

Variant 18-63318646-T-C is Benign according to our data. Variant chr18-63318646-T-C is described in ClinVar as [Benign]. Clinvar id is 3060318.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.699 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL2	NM_000633.3 linkuse as main transcript	c.21A>G	p.Thr7=	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 linkuse as main transcript	c.21A>G	p.Thr7=	synonymous_variant	2/3	1	NM_000633.3	ENSP00000329623	P1	P10415-1

Frequencies

GnomAD3 genomes

AF:

0.318

AC:

48421

AN:

152080

Hom.:

9644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0808

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.349

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.434

Gnomad OTH

AF:

0.354

GnomAD3 exomes

AF:

0.372

AC:

91756

AN:

246918

Hom.:

18853

AF XY:

0.378

AC XY:

50836

AN XY:

134404

show subpopulations

Gnomad AFR exome

AF:

0.0754

Gnomad AMR exome

AF:

0.415

Gnomad ASJ exome

AF:

0.351

Gnomad EAS exome

AF:

0.0968

Gnomad SAS exome

AF:

0.365

Gnomad FIN exome

AF:

0.459

Gnomad NFE exome

AF:

0.427

Gnomad OTH exome

AF:

0.403

GnomAD4 exome

AF:

0.406

AC:

593323

AN:

1459826

Hom.:

125536

Cov.:

AF XY:

0.407

AC XY:

295512

AN XY:

726246

show subpopulations

Gnomad4 AFR exome

AF:

0.0680

Gnomad4 AMR exome

AF:

0.414

Gnomad4 ASJ exome

AF:

0.347

Gnomad4 EAS exome

AF:

0.105

Gnomad4 SAS exome

AF:

0.368

Gnomad4 FIN exome

AF:

0.459

Gnomad4 NFE exome

AF:

0.431

Gnomad4 OTH exome

AF:

0.371

GnomAD4 genome

AF:

0.318

AC:

48426

AN:

152198

Hom.:

9647

Cov.:

AF XY:

0.320

AC XY:

23836

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0805

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.349

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.346

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.434

Gnomad4 OTH

AF:

0.350

Alfa

AF:

0.400

Hom.:

17179

Bravo

AF:

0.303

Asia WGS

AF:

0.202

AC:

705

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

Oct 16, 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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

8.2

DANN

Benign

0.77

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