1-85276329-GAG-TAA

Variant names:

• chr1-85276329-GAG-TAA
• NM_003921.5:c.22_24delCTCinsTTA
• BCL10 p.9

Variant summary

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

The NM_003921.5(BCL10):​c.22_24delCTCinsTTA​(p.9) variant causes a synonymous 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 MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: 5.62
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.22_24delCTCinsTTA	p.9	synonymous	N/A	NP_003912.1	O95999
	BCL10	NM_001320715.2		c.22_24delCTCinsTTA	p.9	synonymous	N/A	NP_001307644.1	A0A087WWW9
	BCL10-AS1	NR_045484.1		n.-29_-27delGAGinsTAA		upstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL10	ENST00000648566.1	MANE Select	c.22_24delCTCinsTTA	p.9	synonymous	N/A	ENSP00000498104.1	O95999
	BCL10	ENST00000913809.1		c.22_24delCTCinsTTA	p.9	synonymous	N/A	ENSP00000583868.1
	BCL10	ENST00000620248.3	TSL:5	c.22_24delCTCinsTTA	p.9	synonymous	N/A	ENSP00000480561.2	A0A087WWW9

Frequencies

GnomAD3 genomes Cov.: 34

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

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.6

Splicing

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;