18-58716960-T-G

Variant names:

• chr18-58716960-T-G
• rs7238078
• NM_006785.4:c.1018+993T>G

Variant summary

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

The NM_006785.4(MALT1):​c.1018+993T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,128 control chromosomes in the GnomAD database, including 4,574 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 0.24 (4574 hom., cov: 32)
• Consequence: MALT1 NM_006785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.943
• Publications: 50 publications found

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 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to MALT1 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics

ENSG00000267476 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.26 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALT1	NM_006785.4	MANE Select	c.1018+993T>G		intron	N/A	NP_006776.1	Q9UDY8-1
	MALT1	NM_173844.3		c.985+993T>G		intron	N/A	NP_776216.1	Q9UDY8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MALT1	ENST00000649217.2	MANE Select	c.1018+993T>G		intron	N/A	ENSP00000497997.1	Q9UDY8-1
	MALT1	ENST00000345724.7	TSL:1	c.985+993T>G		intron	N/A	ENSP00000304161.3	Q9UDY8-2
	MALT1	ENST00000968608.1		c.1141+993T>G		intron	N/A	ENSP00000638667.1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36863 AN: 152010 Hom.: 4571 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.179

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.300

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.260

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.265

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

GnomAD4 genome AF: 0.242 AC: 36890 AN: 152128 Hom.: 4574 Cov.: 32 AF XY: 0.243 AC XY: 18079 AN XY: 74366

African (AFR) AF: 0.259 AC: 10760 AN: 41504

American (AMR) AF: 0.266 AC: 4070 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3466

East Asian (EAS) AF: 0.178 AC: 925 AN: 5186

South Asian (SAS) AF: 0.260 AC: 1253 AN: 4820

European-Finnish (FIN) AF: 0.214 AC: 2256 AN: 10558

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15766 AN: 68000

Other (OTH) AF: 0.264 AC: 557 AN: 2110

Alfa AF: 0.236 Hom.: 19864

Bravo AF: 0.253

Asia WGS AF: 0.219 AC: 763 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.84
PhyloP100		0.94
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: rs7238078; hg19: chr18-56384192;