rs4940736

Positions:

• chr18-58678199-T-A

Variant summary

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

The NM_006785.4(MALT1):​c.210-2971T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 152,152 control chromosomes in the GnomAD database, including 1,622 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 0.12 (1622 hom., cov: 33)
• Consequence: MALT1 NM_006785.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MALT1	NM_006785.4	c.210-2971T>A		intron_variant		ENST00000649217.2
LOC105372146	XR_935537.3	n.257+2273A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MALT1	ENST00000649217.2	c.210-2971T>A		intron_variant			NM_006785.4	P3
	ENST00000588835.1	n.148-5340A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17945 AN: 152034 Hom.: 1619 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0236

Gnomad EAS AF: 0.0714

Gnomad SAS AF: 0.0143

Gnomad FIN AF: 0.122

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.0877

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

GnomAD4 genome AF: 0.118 AC: 17982 AN: 152152 Hom.: 1622 Cov.: 33 AF XY: 0.119 AC XY: 8841 AN XY: 74392

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.0796

Gnomad4 ASJ AF: 0.0236

Gnomad4 EAS AF: 0.0714

Gnomad4 SAS AF: 0.0145

Gnomad4 FIN AF: 0.122

Gnomad4 NFE AF: 0.0591

Gnomad4 OTH AF: 0.0892

Alfa AF: 0.101 Hom.: 129

Bravo AF: 0.123

Asia WGS AF: 0.0770 AC: 267 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.4
DANN	Benign	0.82

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: rs4940736; hg19: chr18-56345431;