Genetic Variant NM_003921.5:c.24C>G (chr1-85276329-G-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003921.5(BCL10):c.24C>G(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 1,613,778 control chromosomes in the GnomAD database, including 71,913 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6012 hom., cov: 34)

Exomes 𝑓: 0.30 ( 65901 hom. )

Consequence

BCL10
NM_003921.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.122

Publications

26 publications found

Variant links:

Genes affected

BCL10 (HGNC:989): (BCL10 immune signaling adaptor) This gene was identified by its translocation in a case of mucosa-associated lymphoid tissue (MALT) lymphoma. The protein encoded by this gene contains a caspase recruitment domain (CARD), and has been shown to induce apoptosis and to activate NF-kappaB. This protein is reported to interact with other CARD domain containing proteins including CARD9, 10, 11 and 14, which are thought to function as upstream regulators in NF-kappaB signaling. This protein is found to form a complex with MALT1, a protein encoded by another gene known to be translocated in MALT lymphoma. MALT1 and this protein are thought to synergize in the activation of NF-kappaB, and the deregulation of either of them may contribute to the same pathogenetic process that leads to the malignancy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2016]

BCL10 links:

BCL10-AS1 (HGNC:55868): (BCL10 antisense RNA 1)

BCL10-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 1-85276329-G-C is Benign according to our data. Variant chr1-85276329-G-C is described in ClinVar as Benign. ClinVar VariationId is 402411.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.122 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003921.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL10	NM_003921.5	MANE Select	c.24C>G	p.Leu8Leu	synonymous	Exon 1 of 3	NP_003912.1	O95999
BCL10	NM_001320715.2		c.24C>G	p.Leu8Leu	synonymous	Exon 1 of 3	NP_001307644.1	A0A087WWW9
BCL10-AS1	NR_045484.1		n.-29G>C		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BCL10	ENST00000648566.1	MANE Select	c.24C>G	p.Leu8Leu	synonymous	Exon 1 of 3	ENSP00000498104.1	O95999
BCL10	ENST00000913809.1		c.24C>G	p.Leu8Leu	synonymous	Exon 1 of 3	ENSP00000583868.1
BCL10	ENST00000620248.3	TSL:5	c.24C>G	p.Leu8Leu	synonymous	Exon 1 of 3	ENSP00000480561.2	A0A087WWW9

Frequencies

GnomAD3 genomes

AF:

0.276

AC:

42027

AN:

152038

Hom.:

6009

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.373

Gnomad AMR

AF:

0.236

Gnomad ASJ

AF:

0.334

Gnomad EAS

AF:

0.0749

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.310

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.311

Gnomad OTH

AF:

0.288

GnomAD2 exomes

AF:

0.271

AC:

67690

AN:

249826

AF XY:

0.275

show subpopulations

Gnomad AFR exome

AF:

0.247

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.332

Gnomad EAS exome

AF:

0.0761

Gnomad FIN exome

AF:

0.316

Gnomad NFE exome

AF:

0.315

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.296

AC:

432591

AN:

1461622

Hom.:

65901

Cov.:

AF XY:

0.297

AC XY:

215760

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.241

AC:

8070

AN:

33470

American (AMR)

AF:

0.196

AC:

8780

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

8684

AN:

26130

East Asian (EAS)

AF:

0.0803

AC:

3188

AN:

39682

South Asian (SAS)

AF:

0.278

AC:

23968

AN:

86250

European-Finnish (FIN)

AF:

0.318

AC:

17003

AN:

53398

Middle Eastern (MID)

AF:

0.323

AC:

1861

AN:

5760

European-Non Finnish (NFE)

AF:

0.309

AC:

343745

AN:

1111838

Other (OTH)

AF:

0.286

AC:

17292

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

16871

33743

50614

67486

84357

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11082

22164

33246

44328

55410

<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:

0.276

AC:

42055

AN:

152156

Hom.:

6012

Cov.:

AF XY:

0.274

AC XY:

20390

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.245

AC:

10186

AN:

41532

American (AMR)

AF:

0.235

AC:

3601

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.334

AC:

1156

AN:

3466

East Asian (EAS)

AF:

0.0750

AC:

387

AN:

5158

South Asian (SAS)

AF:

0.258

AC:

1244

AN:

4820

European-Finnish (FIN)

AF:

0.310

AC:

3284

AN:

10586

Middle Eastern (MID)

AF:

0.288

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.311

AC:

21164

AN:

67986

Other (OTH)

AF:

0.289

AC:

609

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1638

3276

4915

6553

8191

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.310

Hom.:

2434

Bravo

AF:

0.270

Asia WGS

AF:

0.197

AC:

689

AN:

3478

EpiCase

AF:

0.311

EpiControl

AF:

0.314

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Immunodeficiency 37 (1)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.83

PhyloP100

0.12

PromoterAI

0.067

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over