chr18-58749237-A-G

Position:

• chr18-58749237-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006785.4(MALT1):​c.*1395A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 216,282 control chromosomes in the GnomAD database, including 2,304 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 0.13 (2029 hom., cov: 33)
  • Exomes 𝑓: 0.070 (275 hom.)
• Consequence: MALT1 NM_006785.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALT1	NM_006785.4	c.*1395A>G		3_prime_UTR_variant	17/17	ENST00000649217.2
LOC105372146	XR_935537.3	n.61+30921T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALT1	ENST00000649217.2	c.*1395A>G		3_prime_UTR_variant	17/17		NM_006785.4	P3
	ENST00000588835.1	n.56+3438T>C		intron_variant, non_coding_transcript_variant		5
MALT1	ENST00000697046.1	n.3754A>G		non_coding_transcript_exon_variant	10/10
MALT1	ENST00000587438.2			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19522 AN: 152100 Hom.: 2026 Cov.: 33

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0843

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.0717

Gnomad SAS AF: 0.0147

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0595

Gnomad OTH AF: 0.0995

GnomAD4 exome AF: 0.0702 AC: 4496 AN: 64064 Hom.: 275 Cov.: 0 AF XY: 0.0673 AC XY: 1993 AN XY: 29610

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.0887

Gnomad4 ASJ exome AF: 0.0263

Gnomad4 EAS exome AF: 0.0780

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.0538

Gnomad4 OTH exome AF: 0.0784

GnomAD4 genome AF: 0.129 AC: 19561 AN: 152218 Hom.: 2029 Cov.: 33 AF XY: 0.129 AC XY: 9609 AN XY: 74432

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.0844

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.0716

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0595

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0609 Hom.: 427

Bravo AF: 0.135

Asia WGS AF: 0.0800 AC: 280 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.79
DANN	Benign	0.54

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: rs2319974; hg19: chr18-56416469;