rs56142402

Variant names:

• chr18-58671560-G-A
• rs56142402
• ENST00000649217:c.-84G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006785.4(MALT1):​c.-84G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0457 in 926,772 control chromosomes in the GnomAD database, including 1,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (120 hom., cov: 33)
  • Exomes 𝑓: 0.048 (1006 hom.)
• Consequence: MALT1 NM_006785.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.422

Genes affected

MALT1 (HGNC:6819): (MALT1 paracaspase) This gene encodes a caspase-like protease that plays a role in BCL10-induced activation of NF-kappaB. The protein is a component of the CARMA1-BCL10-MALT1 (CBM) signalosome that triggers NF-kappaB signaling and lymphoctye activation following antigen-receptor stimulation. Mutations in this gene result in immunodeficiency 12 (IMD12). This gene has been found to be recurrently rearranged in chromosomal translocations with other genes in mucosa-associated lymphoid tissue lymphomas, including a t(11;18)(q21;q21) translocation with the baculoviral IAP repeat-containing protein 3 (also known as apoptosis inhibitor 2) locus [BIRC3(API2)-MALT1], and a t(14;18)(q32;q21) translocation with the immunoglobulin heavy chain locus (IGH-MALT1). Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, May 2018]

MALT1-AS1 (HGNC:55306): (MALT1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 18-58671560-G-A is Benign according to our data. Variant chr18-58671560-G-A is described in ClinVar as [Benign]. Clinvar id is 403068.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALT1	NM_006785.4	c.-84G>A		5_prime_UTR_variant	Exon 1 of 17	ENST00000649217.2	NP_006776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALT1	ENST00000649217	c.-84G>A		5_prime_UTR_variant	Exon 1 of 17		NM_006785.4	ENSP00000497997.1

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5167 AN: 151806 Hom.: 121 Cov.: 33

Gnomad AFR AF: 0.00898

Gnomad AMI AF: 0.0639

Gnomad AMR AF: 0.0368

Gnomad ASJ AF: 0.0364

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0987

Gnomad NFE AF: 0.0526

Gnomad OTH AF: 0.0447

GnomAD4 exome AF: 0.0479 AC: 37146 AN: 774858 Hom.: 1006 Cov.: 11 AF XY: 0.0478 AC XY: 17747 AN XY: 371324

Gnomad4 AFR exome AF: 0.00748

Gnomad4 AMR exome AF: 0.0309

Gnomad4 ASJ exome AF: 0.0374

Gnomad4 EAS exome AF: 0.0000867

Gnomad4 SAS exome AF: 0.0141

Gnomad4 FIN exome AF: 0.0287

Gnomad4 NFE exome AF: 0.0522

Gnomad4 OTH exome AF: 0.0475

GnomAD4 genome AF: 0.0340 AC: 5162 AN: 151914 Hom.: 120 Cov.: 33 AF XY: 0.0331 AC XY: 2462 AN XY: 74272

Gnomad4 AFR AF: 0.00898

Gnomad4 AMR AF: 0.0367

Gnomad4 ASJ AF: 0.0364

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0159

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0526

Gnomad4 OTH AF: 0.0442

Alfa AF: 0.0434 Hom.: 21

Bravo AF: 0.0323

Asia WGS AF: 0.00922 AC: 32 AN: 3376

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	14
DANN	Benign	0.96

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: rs56142402; hg19: chr18-56338792;