rs4949928

Variant names:

• chr1-85276001-T-C
• rs4949928
• NM_003921.5:c.57+295A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-85276001-T-C
• chr1-85276001-T-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+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
• Publications: 7 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.308 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+295A>G		intron	N/A	NP_003912.1
	BCL10	NM_001320715.2		c.57+295A>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+295A>G		intron	N/A	ENSP00000498104.1
	BCL10	ENST00000649060.1		n.*109A>G		non_coding_transcript_exon	Exon 1 of 2	ENSP00000497490.1
	BCL10	ENST00000649060.1		n.*109A>G		3_prime_UTR	Exon 1 of 2	ENSP00000497490.1

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

African (AFR) AF: 0.248 AC: 10300 AN: 41498

American (AMR) AF: 0.236 AC: 3604 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3470

East Asian (EAS) AF: 0.0751 AC: 389 AN: 5182

South Asian (SAS) AF: 0.259 AC: 1245 AN: 4814

European-Finnish (FIN) AF: 0.310 AC: 3273 AN: 10548

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21190 AN: 67984

Other (OTH) AF: 0.290 AC: 613 AN: 2114

Alfa AF: 0.251 Hom.: 1210

Bravo AF: 0.270

Asia WGS AF: 0.197 AC: 688 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		-1.9
PromoterAI		0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4949928; hg19: chr1-85741684;