1-85267691-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 13/19 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.257

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
BCL10	NM_003921.5	c.638G>A	p.Gly213Glu	missense_variant	3/3	ENST00000648566.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BCL10	ENST00000648566.1	c.638G>A	p.Gly213Glu	missense_variant	3/3		NM_003921.5	P1
BCL10	ENST00000620248.3	c.605G>A	p.Gly202Glu	missense_variant	3/3	5
BCL10	ENST00000650582.1			downstream_gene_variant

Frequencies

GnomAD3 genomes AF: 0.0473 AC: 7199 AN: 152162 Hom.: 251 Cov.: 33

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

GnomAD3 exomes AF: 0.0651 AC: 16344 AN: 251142 Hom.: 680 AF XY: 0.0660 AC XY: 8954 AN XY: 135760

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 SAS exome AF: 0.0931

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.: 31 AF XY: 0.0610 AC XY: 44361 AN XY: 727126

Gnomad4 AFR exome AF: 0.00989

Gnomad4 AMR exome AF: 0.0751

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.0888

Gnomad4 FIN exome AF: 0.0475

Gnomad4 NFE exome AF: 0.0569

Gnomad4 OTH exome AF: 0.0622

GnomAD4 genome AF: 0.0473 AC: 7199 AN: 152280 Hom.: 250 Cov.: 33 AF XY: 0.0474 AC XY: 3530 AN XY: 74460

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0608

Gnomad4 ASJ AF: 0.0254

Gnomad4 EAS AF: 0.153

Gnomad4 SAS AF: 0.0896

Gnomad4 FIN AF: 0.0463

Gnomad4 NFE AF: 0.0550

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0507 Hom.: 109

Bravo AF: 0.0466

TwinsUK AF: 0.0558 AC: 207

ALSPAC AF: 0.0651 AC: 251

ESP6500AA AF: 0.0132 AC: 58

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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 -

Immunodeficiency 37 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	18
Dann	Uncertain	0.99
DEOGEN2	Benign	0.38	T;T;.
Eigen	Benign	-0.88
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.25	N
MetaRNN	Benign	0.0012	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-1.0	N;N;.
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.39	T
Polyphen		0.0	B;B;.
Vest4		0.058
MPC		1.0
ClinPred		0.0061	T
GERP RS		-0.91
Varity_R		0.11
gMVP		0.35

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

Other links and lift over

dbSNP: rs3768235; hg19: chr1-85733374; COSMIC: COSV65353501; COSMIC: COSV65353501;