1-85276329-G-C

Variant names:

• chr1-85276329-G-C
• rs11576939
• NM_003921.5:c.24C>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.122
• Publications: 26 publications found

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

ACMG classification

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

Selected	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
	BCL10	NM_001320715.2		c.24C>G	p.Leu8Leu	synonymous	Exon 1 of 3	NP_001307644.1
	BCL10-AS1	NR_045484.1		n.-29G>C		upstream_gene	N/A

Ensembl Transcripts

Selected	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
	BCL10	ENST00000620248.3	TSL:5	c.24C>G	p.Leu8Leu	synonymous	Exon 1 of 3	ENSP00000480561.2
	BCL10	ENST00000649060.1		n.24C>G		non_coding_transcript_exon	Exon 1 of 2	ENSP00000497490.1

Frequencies

GnomAD3 genomes AF: 0.276 AC: 42027 AN: 152038 Hom.: 6009 Cov.: 34

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

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.: 47 AF XY: 0.297 AC XY: 215760 AN XY: 727128

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

GnomAD4 genome AF: 0.276 AC: 42055 AN: 152156 Hom.: 6012 Cov.: 34 AF XY: 0.274 AC XY: 20390 AN XY: 74380

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: 84 AN: 292

European-Non Finnish (NFE) AF: 0.311 AC: 21164 AN: 67986

Other (OTH) AF: 0.289 AC: 609 AN: 2108

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

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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: Associated with advanced germ cell tumors, unrelated to patient disease

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	10
DANN	Benign	0.83
PhyloP100		0.12
PromoterAI		0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11576939; hg19: chr1-85742012; COSMIC: COSV65353426; COSMIC: COSV65353426;