NM_003921.5:c.58-1719G>A

Variant names:

• chr1-85272625-C-T
• rs12134420
• NM_003921.5:c.58-1719G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003921.5(BCL10):​c.58-1719G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 151,936 control chromosomes in the GnomAD database, including 3,038 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 0.20 (3038 hom., cov: 30)
• Consequence: BCL10 NM_003921.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.30
• Publications: 12 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BCL10	NM_003921.5	c.58-1719G>A		intron_variant	Intron 1 of 2	ENST00000648566.1	NP_003912.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BCL10	ENST00000648566.1	c.58-1719G>A		intron_variant	Intron 1 of 2		NM_003921.5	ENSP00000498104.1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30066 AN: 151818 Hom.: 3036 Cov.: 30

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.198 AC: 30063 AN: 151936 Hom.: 3038 Cov.: 30 AF XY: 0.199 AC XY: 14776 AN XY: 74268

African (AFR) AF: 0.203 AC: 8398 AN: 41408

American (AMR) AF: 0.209 AC: 3194 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 450 AN: 3468

East Asian (EAS) AF: 0.145 AC: 748 AN: 5170

South Asian (SAS) AF: 0.117 AC: 563 AN: 4814

European-Finnish (FIN) AF: 0.236 AC: 2479 AN: 10512

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13676 AN: 67970

Other (OTH) AF: 0.182 AC: 384 AN: 2114

Alfa AF: 0.197 Hom.: 4122

Bravo AF: 0.197

Asia WGS AF: 0.105 AC: 364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.62
PhyloP100		-1.3
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: rs12134420; hg19: chr1-85738308;