1-85276001-T-C

Position:

• chr1-85276001-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003921.5(BCL10):​c.57+295A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.277 in 152,100 control chromosomes in the GnomAD database, including 6,047 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6047 hom., cov: 33)
• Consequence: BCL10 NM_003921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL10	NM_003921.5	c.57+295A>G		intron_variant		ENST00000648566.1	NP_003912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL10	ENST00000648566.1	c.57+295A>G		intron_variant			NM_003921.5	ENSP00000498104.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42160 AN: 151982 Hom.: 6044 Cov.: 33

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.0749

Gnomad SAS AF: 0.259

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.277 AC: 42191 AN: 152100 Hom.: 6047 Cov.: 33 AF XY: 0.275 AC XY: 20442 AN XY: 74332

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.236

Gnomad4 ASJ AF: 0.333

Gnomad4 EAS AF: 0.0751

Gnomad4 SAS AF: 0.259

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.290

Alfa AF: 0.174 Hom.: 341

Bravo AF: 0.270

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs4949928; hg19: chr1-85741684;