Variant 18-58671560-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.422

Variant links:

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 links:

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

MALT1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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/exons	MANE	Protein	UniProt
MALT1	NM_006785.4 linkuse as main transcript	c.-84G>A		5_prime_UTR_variant	1/17	ENST00000649217.2	NP_006776.1
MALT1-AS1	NR_164150.1 linkuse as main transcript	n.314C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MALT1	ENST00000649217.2 linkuse as main transcript	c.-84G>A	5_prime_UTR_variant	1/17		NM_006785.4	ENSP00000497997	P3	Q9UDY8-1
MALT1	ENST00000345724.7 linkuse as main transcript	c.-84G>A	5_prime_UTR_variant	1/16	1		ENSP00000304161	A2	Q9UDY8-2
MALT1-AS1	ENST00000588144.2 linkuse as main transcript	n.318C>T	non_coding_transcript_exon_variant	1/2	2
MALT1	ENST00000650045.1 linkuse as main transcript		upstream_gene_variant				ENSP00000497036

Frequencies

GnomAD3 genomes

AF:

0.0340

AC:

5167

AN:

151806

Hom.:

121

Cov.:

show subpopulations

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.:

AF XY:

0.0478

AC XY:

17747

AN XY:

371324

show subpopulations

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.:

AF XY:

0.0331

AC XY:

2462

AN XY:

74272

show subpopulations

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.:

Bravo

AF:

0.0323

Asia WGS

AF:

0.00922

AC:

AN:

3376

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

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

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over