Genetic Variant BCL2L12:c.*166G>A (chr19-49673914-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_138639.2(BCL2L12):c.*166G>A variant causes a splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 686,808 control chromosomes in the GnomAD database, including 3,387 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.072 ( 517 hom., cov: 32)

Exomes 𝑓: 0.097 ( 2870 hom. )

Consequence

BCL2L12
NM_138639.2 splice_region

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.270

Publications

20 publications found

Variant links:

Genes affected

BCL2L12 (HGNC:13787): (BCL2 like 12) This gene encodes a member of a family of proteins containing a Bcl-2 homology domain 2 (BH2). The encoded protein is an anti-apoptotic factor that acts as an inhibitor of caspases 3 and 7 in the cytoplasm. In the nucleus, it binds to the p53 tumor suppressor protein, preventing its association with target genes. Overexpression of this gene has been detected in a number of different cancers. There is a pseudogene for this gene on chromosome 3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

BCL2L12 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL2L12	NM_138639.2 link	c.*166G>A		splice_region_variant	Exon 7 of 7	ENST00000246784.8	NP_619580.2	Q9HB09
BCL2L12	NM_138639.2 link	c.*166G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000246784.8	NP_619580.2	Q9HB09

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL2L12	ENST00000246784.8 link	c.*166G>A		splice_region_variant	Exon 7 of 7	1	NM_138639.2	ENSP00000246784.4		A0A087WSV0
BCL2L12	ENST00000246784.8 link	c.*166G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_138639.2	ENSP00000246784.4		A0A087WSV0

Frequencies

GnomAD3 genomes

AF:

0.0720

AC:

10959

AN:

152160

Hom.:

518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0191

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.0651

Gnomad ASJ

AF:

0.105

Gnomad EAS

AF:

0.0850

Gnomad SAS

AF:

0.166

Gnomad FIN

AF:

0.0535

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0979

Gnomad OTH

AF:

0.0833

GnomAD4 exome

AF:

0.0968

AC:

51725

AN:

534530

Hom.:

2870

Cov.:

AF XY:

0.100

AC XY:

27487

AN XY:

274868

show subpopulations

African (AFR)

AF:

0.0191

AC:

270

AN:

14172

American (AMR)

AF:

0.0560

AC:

1023

AN:

18278

Ashkenazi Jewish (ASJ)

AF:

0.108

AC:

1461

AN:

13504

East Asian (EAS)

AF:

0.0750

AC:

2243

AN:

29916

South Asian (SAS)

AF:

0.169

AC:

6682

AN:

39570

European-Finnish (FIN)

AF:

0.0692

AC:

2214

AN:

31990

Middle Eastern (MID)

AF:

0.198

AC:

697

AN:

3512

European-Non Finnish (NFE)

AF:

0.0969

AC:

34503

AN:

356074

Other (OTH)

AF:

0.0957

AC:

2632

AN:

27514

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

2208

4416

6623

8831

11039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

746

1492

2238

2984

3730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0720

AC:

10959

AN:

152278

Hom.:

517

Cov.:

AF XY:

0.0726

AC XY:

5406

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.0190

AC:

791

AN:

41562

American (AMR)

AF:

0.0652

AC:

997

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.105

AC:

366

AN:

3472

East Asian (EAS)

AF:

0.0847

AC:

439

AN:

5186

South Asian (SAS)

AF:

0.165

AC:

794

AN:

4826

European-Finnish (FIN)

AF:

0.0535

AC:

568

AN:

10608

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0980

AC:

6663

AN:

68024

Other (OTH)

AF:

0.0853

AC:

180

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

518

1036

1553

2071

2589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

138

276

414

552

690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0895

Hom.:

2366

Bravo

AF:

0.0670

Asia WGS

AF:

0.169

AC:

584

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.48

(source)

DANN

Benign

0.51

PhyloP100

-0.27

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over