rs56142402

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

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

new If you want to explore the variant's impact on the transcript NM_006785.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006785.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MALT1	NM_006785.4	MANE Select	c.-84G>A	5_prime_UTR	Exon 1 of 17	NP_006776.1	Q9UDY8-1
MALT1	NM_173844.3		c.-84G>A	5_prime_UTR	Exon 1 of 16	NP_776216.1	Q9UDY8-2
MALT1-AS1	NR_164150.1		n.314C>T	non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MALT1	ENST00000649217.2	MANE Select	c.-84G>A	5_prime_UTR	Exon 1 of 17	ENSP00000497997.1	Q9UDY8-1
MALT1	ENST00000345724.7	TSL:1	c.-84G>A	5_prime_UTR	Exon 1 of 16	ENSP00000304161.3	Q9UDY8-2
MALT1	ENST00000968608.1		c.-84G>A	5_prime_UTR	Exon 1 of 18	ENSP00000638667.1

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

African (AFR)

AF:

0.00748

AC:

123

AN:

16438

American (AMR)

AF:

0.0309

AC:

218

AN:

7060

Ashkenazi Jewish (ASJ)

AF:

0.0374

AC:

418

AN:

11182

East Asian (EAS)

AF:

0.0000867

AC:

AN:

23076

South Asian (SAS)

AF:

0.0141

AC:

183

AN:

12982

European-Finnish (FIN)

AF:

0.0287

AC:

583

AN:

20298

Middle Eastern (MID)

AF:

0.0871

AC:

195

AN:

2240

European-Non Finnish (NFE)

AF:

0.0522

AC:

33885

AN:

649198

Other (OTH)

AF:

0.0475

AC:

1539

AN:

32384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1774

3549

5323

7098

8872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1376

2752

4128

5504

6880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0340

AC:

5162

AN:

151914

Hom.:

120

Cov.:

AF XY:

0.0331

AC XY:

2462

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.00898

AC:

373

AN:

41534

American (AMR)

AF:

0.0367

AC:

560

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.0364

AC:

126

AN:

3466

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.0159

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0265

AC:

278

AN:

10476

Middle Eastern (MID)

AF:

0.0925

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0526

AC:

3568

AN:

67884

Other (OTH)

AF:

0.0442

AC:

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

262

525

787

1050

1312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0434

Hom.:

Bravo

AF:

0.0323

Asia WGS

AF:

0.00922

AC:

AN:

3376

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

0.42

PromoterAI

-0.18

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over