chr1-85267787-CTGCCTACTTCTAGAACA-C

Variant names:

• chr1-85267787-CTGCCTACTTCTAGAACA-C
• rs587776634
• NM_003921.5:c.525_541delTGTTCTAGAAGTAGGCA

Variant summary

Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PVS1_Strong PP5

The NM_003921.5(BCL10):​c.525_541delTGTTCTAGAAGTAGGCA​(p.Val176AsnfsTer2) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: BCL10 NM_003921.5 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 4.21
• Publications: 1 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 Gene-Disease associations (from GenCC):

• immunodeficiency 37

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 5 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.252 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
• PP5: Variant 1-85267787-CTGCCTACTTCTAGAACA-C is Pathogenic according to our data. Variant chr1-85267787-CTGCCTACTTCTAGAACA-C is described in ClinVar as [Pathogenic]. Clinvar id is 6255.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL10	NM_003921.5	c.525_541delTGTTCTAGAAGTAGGCA	p.Val176AsnfsTer2	frameshift_variant	Exon 3 of 3	ENST00000648566.1	NP_003912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL10	ENST00000648566.1	c.525_541delTGTTCTAGAAGTAGGCA	p.Val176AsnfsTer2	frameshift_variant	Exon 3 of 3		NM_003921.5	ENSP00000498104.1
BCL10	ENST00000620248.3	c.492_508delTGTTCTAGAAGTAGGCA	p.Val165AsnfsTer2	frameshift_variant	Exon 3 of 3	5		ENSP00000480561.2
BCL10	ENST00000650582.1	n.1056_1072delTGTTCTAGAAGTAGGCA		non_coding_transcript_exon_variant	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Follicular lymphoma Pathogenic:1

Jan 08, 1999

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.2
Mutation Taster		=12/188	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587776634; hg19: chr1-85733470;