rs558928879

Variant names:

• chr18-58733376-TCTTA-T
• rs558928879
• NM_006785.4:c.1223-20_1223-17delCTTA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_006785.4(MALT1):​c.1223-20_1223-17delCTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00794 in 1,533,728 control chromosomes in the GnomAD database, including 63 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0053 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0082 (58 hom.)
• Consequence: MALT1 NM_006785.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.09

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]

ENSG00000267476 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 18-58733376-TCTTA-T is Benign according to our data. Variant chr18-58733376-TCTTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 445912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00534 (813/152324) while in subpopulation NFE AF= 0.00919 (625/68006). AF 95% confidence interval is 0.00859. There are 5 homozygotes in gnomad4. There are 369 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MALT1	NM_006785.4	c.1223-20_1223-17delCTTA		intron_variant	Intron 10 of 16	ENST00000649217.2	NP_006776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALT1	ENST00000649217.2	c.1223-20_1223-17delCTTA		intron_variant	Intron 10 of 16		NM_006785.4	ENSP00000497997.1

Frequencies

GnomAD3 genomes AF: 0.00535 AC: 814 AN: 152206 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00145

Gnomad AMI AF: 0.0175

Gnomad AMR AF: 0.00170

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00920

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00560 AC: 1265 AN: 226088 Hom.: 7 AF XY: 0.00588 AC XY: 719 AN XY: 122302

Gnomad AFR exome AF: 0.00139

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.00143

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00309

Gnomad FIN exome AF: 0.00563

Gnomad NFE exome AF: 0.00894

Gnomad OTH exome AF: 0.00684

GnomAD4 exome AF: 0.00823 AC: 11366 AN: 1381404 Hom.: 58 AF XY: 0.00796 AC XY: 5497 AN XY: 690228

Gnomad4 AFR exome AF: 0.00118

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.00124

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00290

Gnomad4 FIN exome AF: 0.00557

Gnomad4 NFE exome AF: 0.00977

Gnomad4 OTH exome AF: 0.00640

GnomAD4 genome AF: 0.00534 AC: 813 AN: 152324 Hom.: 5 Cov.: 33 AF XY: 0.00495 AC XY: 369 AN XY: 74492

Gnomad4 AFR AF: 0.00144

Gnomad4 AMR AF: 0.00170

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00565

Gnomad4 NFE AF: 0.00919

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00560 Hom.: 0

Bravo AF: 0.00527

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Combined immunodeficiency due to MALT1 deficiency Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 14, 2022

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 03, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Jun 14, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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: rs558928879; hg19: chr18-56400608;