rs4949927

Variant names:

• chr1-85274341-T-C
• rs4949927
• NM_003921.5:c.57+1955A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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: Benign. The variant received -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL10	NM_003921.5	MANE Select	c.57+1955A>G		intron	N/A	NP_003912.1
	BCL10	NM_001320715.2		c.57+1955A>G		intron	N/A	NP_001307644.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BCL10	ENST00000648566.1	MANE Select	c.57+1955A>G		intron	N/A	ENSP00000498104.1
	BCL10	ENST00000620248.3	TSL:5	c.57+1955A>G		intron	N/A	ENSP00000480561.2
	BCL10	ENST00000649060.1		n.*1166+603A>G		intron	N/A	ENSP00000497490.1

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

African (AFR) AF: 0.235 AC: 9755 AN: 41514

American (AMR) AF: 0.202 AC: 3093 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1060 AN: 3470

East Asian (EAS) AF: 0.0746 AC: 387 AN: 5186

South Asian (SAS) AF: 0.247 AC: 1191 AN: 4830

European-Finnish (FIN) AF: 0.254 AC: 2684 AN: 10580

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.234 AC: 15905 AN: 68006

Other (OTH) AF: 0.247 AC: 521 AN: 2110

Alfa AF: 0.232 Hom.: 14422

Bravo AF: 0.225

Asia WGS AF: 0.189 AC: 660 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4949927; hg19: chr1-85740024;