1-85276329-G-T

Variant names:

• chr1-85276329-G-T
• NM_003921.5:c.24C>A
• BCL10 p.Leu8Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003921.5(BCL10):​c.24C>A​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 34)
• Consequence: BCL10 NM_003921.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.122
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.122 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL10	NM_003921.5	MANE Select	c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 3	NP_003912.1	O95999
	BCL10	NM_001320715.2		c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 3	NP_001307644.1	A0A087WWW9
	BCL10-AS1	NR_045484.1		n.-29G>T		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL10	ENST00000648566.1	MANE Select	c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 3	ENSP00000498104.1	O95999
	BCL10	ENST00000913809.1		c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 3	ENSP00000583868.1
	BCL10	ENST00000620248.3	TSL:5	c.24C>A	p.Leu8Leu	synonymous	Exon 1 of 3	ENSP00000480561.2	A0A087WWW9

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	11
DANN	Benign	0.91
PhyloP100		0.12
PromoterAI		-0.0060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-85742012;