rs4949927

Positions:

• chr1-85274341-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+1955A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 152,182 control chromosomes in the GnomAD database, including 4,069 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 0.23 (4069 hom., cov: 33)
• Consequence: BCL10 NM_003921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.311

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL10	NM_003921.5	c.57+1955A>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+1955A>G		intron_variant			NM_003921.5	ENSP00000498104	P1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34788 AN: 152064 Hom.: 4066 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.0745

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.229 AC: 34821 AN: 152182 Hom.: 4069 Cov.: 33 AF XY: 0.229 AC XY: 17031 AN XY: 74394

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.305

Gnomad4 EAS AF: 0.0746

Gnomad4 SAS AF: 0.247

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.247

Alfa AF: 0.236 Hom.: 6186

Bravo AF: 0.225

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs4949927; hg19: chr1-85740024;