Variant 12-122022184-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP3

The NM_001024808.3(BCL7A):c.92+1G>C variant causes a splice donor, intron change. The variant allele was found at a frequency of 0.00000402 in 1,493,436 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as other (no stars).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

BCL7A
NM_001024808.3 splice_donor, intron

Scores

Splicing: ADA: 1.000

Clinical Significance

- - O:1

Conservation

PhyloP100: 5.71

Variant links:

Genes affected

BCL7A (HGNC:1004): (BAF chromatin remodeling complex subunit BCL7A) This gene is directly involved, with Myc and IgH, in a three-way gene translocation in a Burkitt lymphoma cell line. As a result of the gene translocation, the N-terminal region of the gene product is disrupted, which is thought to be related to the pathogenesis of a subset of high-grade B cell non-Hodgkin lymphoma. The N-terminal segment involved in the translocation includes the region that shares a strong sequence similarity with those of BCL7B and BCL7C. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

BCL7A links:

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ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.47235388 fraction of the gene. Cryptic splice site detected, with MaxEntScore 3.9, offset of -11, new splice context is: aaaGTgcgc. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.

PM2

Very rare variant in population databases, with high coverage;

PP3

Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, BayesDel_noAF, MutationTaster was below the threshold]

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL7A	NM_001024808.3 link	c.92+1G>C		splice_donor_variant, intron_variant		ENST00000261822.5	NP_001019979.1	Q4VC05-1
BCL7A	NM_020993.5 link	c.92+1G>C		splice_donor_variant, intron_variant			NP_066273.1	Q4VC05-2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
BCL7A	ENST00000261822.5 link	c.92+1G>C	splice_donor_variant, intron_variant	1	NM_001024808.3	ENSP00000261822.5	Q4VC05-1
BCL7A	ENST00000538010.5 link	c.92+1G>C	splice_donor_variant, intron_variant	1		ENSP00000445868.1	Q4VC05-2
BCL7A	ENST00000432926.2 link	n.206+1G>C	splice_donor_variant, intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0000270

AC:

AN:

147988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000735

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000669

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000689

AC:

AN:

145172

Hom.:

AF XY:

0.0000124

AC XY:

AN XY:

80444

show subpopulations

Gnomad AFR exome

AF:

0.000218

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000149

AC:

AN:

1345346

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

665350

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000190

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000270

AC:

AN:

148090

Hom.:

Cov.:

AF XY:

0.0000415

AC XY:

AN XY:

72220

show subpopulations

Gnomad4 AFR

AF:

0.0000733

Gnomad4 AMR

AF:

0.0000668

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000907

AC:

ClinVar

Significance: -

Submissions summary: Other:1

Revision: -

LINK: link

Submissions by phenotype

Neoplasm

Other:1

-, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Jul 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Pathogenic

0.85

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.78

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.87

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.43

Position offset: -12

DS_DL_spliceai

0.99

Position offset: -1

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