rs12037217

Positions:

chr1-85276340-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003921.5(BCL10):c.13G>T(p.Ala5Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0246 in 1,613,546 control chromosomes in the GnomAD database, including 780 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 93 hom., cov: 34)

Exomes 𝑓: 0.025 ( 687 hom. )

Consequence

BCL10
NM_003921.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.77

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015875101).

BP6

Variant 1-85276340-C-A is Benign according to our data. Variant chr1-85276340-C-A is described in ClinVar as [Benign]. Clinvar id is 475271.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL10	NM_003921.5 linkuse as main transcript	c.13G>T	p.Ala5Ser	missense_variant	1/3	ENST00000648566.1	NP_003912.1
BCL10-AS1	NR_045484.1 linkuse as main transcript			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL10	ENST00000648566.1 linkuse as main transcript	c.13G>T	p.Ala5Ser	missense_variant	1/3		NM_003921.5	ENSP00000498104	P1

Frequencies

GnomAD3 genomes

AF:

0.0232

AC:

3529

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00468

Gnomad AMI

AF:

0.0603

Gnomad AMR

AF:

0.0283

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0247

Gnomad OTH

AF:

0.0369

GnomAD3 exomes

AF:

0.0300

AC:

7512

AN:

250084

Hom.:

246

AF XY:

0.0304

AC XY:

4107

AN XY:

135294

show subpopulations

Gnomad AFR exome

AF:

0.00413

Gnomad AMR exome

AF:

0.0191

Gnomad ASJ exome

AF:

0.0878

Gnomad EAS exome

AF:

0.120

Gnomad SAS exome

AF:

0.0187

Gnomad FIN exome

AF:

0.00453

Gnomad NFE exome

AF:

0.0250

Gnomad OTH exome

AF:

0.0349

GnomAD4 exome

AF:

0.0247

AC:

36149

AN:

1461324

Hom.:

687

Cov.:

AF XY:

0.0251

AC XY:

18212

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00523

Gnomad4 AMR exome

AF:

0.0199

Gnomad4 ASJ exome

AF:

0.0910

Gnomad4 EAS exome

AF:

0.0837

Gnomad4 SAS exome

AF:

0.0199

Gnomad4 FIN exome

AF:

0.00551

Gnomad4 NFE exome

AF:

0.0226

Gnomad4 OTH exome

AF:

0.0314

GnomAD4 genome

AF:

0.0232

AC:

3525

AN:

152222

Hom.:

Cov.:

AF XY:

0.0227

AC XY:

1689

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00467

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.0933

Gnomad4 EAS

AF:

0.114

Gnomad4 SAS

AF:

0.0212

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.0247

Gnomad4 OTH

AF:

0.0389

Alfa

AF:

0.0310

Hom.:

163

Bravo

AF:

0.0255

TwinsUK

AF:

0.0194

AC:

ALSPAC

AF:

0.0197

AC:

ESP6500AA

AF:

0.00409

AC:

ESP6500EA

AF:

0.0284

AC:

244

ExAC

AF:

0.0289

AC:

3508

Asia WGS

AF:

0.0720

AC:

250

AN:

3478

EpiCase

AF:

0.0318

EpiControl

AF:

0.0331

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

BCL10-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 02, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Immunodeficiency 37

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.31

T;T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.73

.;T;T

MetaRNN

Benign

0.0016

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;N;.

MutationTaster

Benign

0.97

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.44

.;N;.

REVEL

Benign

0.039

Sift

Uncertain

0.025

.;D;.

Sift4G

Benign

0.56

.;T;T

Polyphen

0.0

B;B;.

Vest4

0.056, 0.033

MPC

0.72

ClinPred

0.016

GERP RS

3.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.13

gMVP

0.49

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

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