chr1-85267691-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003921.5(BCL10):c.638G>A(p.Gly213Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0591 in 1,613,906 control chromosomes in the GnomAD database, including 3,401 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.047 ( 250 hom., cov: 33)

Exomes 𝑓: 0.060 ( 3151 hom. )

Consequence

BCL10
NM_003921.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.257

Publications

32 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 Gene-Disease associations (from GenCC):

immunodeficiency 37
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

BCL10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0011563003).

BP6

Variant 1-85267691-C-T is Benign according to our data. Variant chr1-85267691-C-T is described in ClinVar as Benign. ClinVar VariationId is 402410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL10	NM_003921.5 link	c.638G>A	p.Gly213Glu	missense_variant	Exon 3 of 3	ENST00000648566.1	NP_003912.1	O95999

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BCL10	ENST00000648566.1 link	c.638G>A	p.Gly213Glu	missense_variant	Exon 3 of 3		NM_003921.5	ENSP00000498104.1	O95999
BCL10	ENST00000620248.3 link	c.605G>A	p.Gly202Glu	missense_variant	Exon 3 of 3	5		ENSP00000480561.2	A0A087WWW9
BCL10	ENST00000650582.1 link	n.*38G>A		downstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.0473

AC:

7199

AN:

152162

Hom.:

251

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.102

Gnomad AMR

AF:

0.0606

Gnomad ASJ

AF:

0.0254

Gnomad EAS

AF:

0.154

Gnomad SAS

AF:

0.0899

Gnomad FIN

AF:

0.0463

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0550

Gnomad OTH

AF:

0.0411

GnomAD2 exomes

AF:

0.0651

AC:

16344

AN:

251142

AF XY:

0.0660

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.0799

Gnomad ASJ exome

AF:

0.0254

Gnomad EAS exome

AF:

0.152

Gnomad FIN exome

AF:

0.0461

Gnomad NFE exome

AF:

0.0543

Gnomad OTH exome

AF:

0.0586

GnomAD4 exome

AF:

0.0603

AC:

88113

AN:

1461626

Hom.:

3151

Cov.:

AF XY:

0.0610

AC XY:

44361

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.00989

AC:

331

AN:

33466

American (AMR)

AF:

0.0751

AC:

3357

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.0257

AC:

671

AN:

26126

East Asian (EAS)

AF:

0.157

AC:

6229

AN:

39684

South Asian (SAS)

AF:

0.0888

AC:

7660

AN:

86218

European-Finnish (FIN)

AF:

0.0475

AC:

2538

AN:

53414

Middle Eastern (MID)

AF:

0.0609

AC:

351

AN:

5762

European-Non Finnish (NFE)

AF:

0.0569

AC:

63221

AN:

1111892

Other (OTH)

AF:

0.0622

AC:

3755

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

4411

8822

13232

17643

22054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2474

4948

7422

9896

12370

<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:

0.0473

AC:

7199

AN:

152280

Hom.:

250

Cov.:

AF XY:

0.0474

AC XY:

3530

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0129

AC:

535

AN:

41564

American (AMR)

AF:

0.0608

AC:

930

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0254

AC:

AN:

3470

East Asian (EAS)

AF:

0.153

AC:

792

AN:

5182

South Asian (SAS)

AF:

0.0896

AC:

432

AN:

4824

European-Finnish (FIN)

AF:

0.0463

AC:

490

AN:

10592

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0550

AC:

3744

AN:

68034

Other (OTH)

AF:

0.0421

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

349

698

1047

1396

1745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0504

Hom.:

109

Bravo

AF:

0.0466

TwinsUK

AF:

0.0558

AC:

207

ALSPAC

AF:

0.0651

AC:

251

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.0566

AC:

487

ExAC

AF:

0.0639

AC:

7761

Asia WGS

AF:

0.141

AC:

488

AN:

3478

EpiCase

AF:

0.0523

EpiControl

AF:

0.0519

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: MAF -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Immunodeficiency 37

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.38

T;T;.

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.64

.;T;T

MetaRNN

Benign

0.0012

T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-1.0

N;N;.

PhyloP100

0.26

PrimateAI

Benign

0.39

PROVEAN

Benign

-1.2

.;N;.

REVEL

Benign

0.057

Sift

Benign

0.37

.;T;.

Sift4G

Benign

0.70

.;T;.

Polyphen

0.0

B;B;.

Vest4

0.058

MPC

1.0

ClinPred

0.0061

GERP RS

-0.91

Varity_R

0.11

gMVP

0.35

Mutation Taster

=97/3

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over