dbSNP rs3745469: 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

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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