rs2319974

Variant names:

• chr18-58749237-A-G
• rs2319974
• NM_006785.4:c.*1395A>G

Your query was ambiguous. Multiple possible variants found:

• chr18-58749237-A-G
• chr18-58749237-A-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen

ENSG00000267476 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MALT1	NM_006785.4	c.*1395A>G		3_prime_UTR_variant	Exon 17 of 17	ENST00000649217.2	NP_006776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MALT1	ENST00000649217.2	c.*1395A>G		3_prime_UTR_variant	Exon 17 of 17		NM_006785.4	ENSP00000497997.1

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

African (AFR) AF: 0.312 AC: 921 AN: 2952

American (AMR) AF: 0.0887 AC: 174 AN: 1962

Ashkenazi Jewish (ASJ) AF: 0.0263 AC: 107 AN: 4068

East Asian (EAS) AF: 0.0780 AC: 717 AN: 9196

South Asian (SAS) AF: 0.0126 AC: 7 AN: 554

European-Finnish (FIN) AF: 0.225 AC: 9 AN: 40

Middle Eastern (MID) AF: 0.0363 AC: 14 AN: 386

European-Non Finnish (NFE) AF: 0.0538 AC: 2123 AN: 39496

Other (OTH) AF: 0.0784 AC: 424 AN: 5410

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

African (AFR) AF: 0.293 AC: 12150 AN: 41512

American (AMR) AF: 0.0844 AC: 1290 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0236 AC: 82 AN: 3472

East Asian (EAS) AF: 0.0716 AC: 372 AN: 5192

South Asian (SAS) AF: 0.0149 AC: 72 AN: 4830

European-Finnish (FIN) AF: 0.122 AC: 1298 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0595 AC: 4048 AN: 68004

Other (OTH) AF: 0.101 AC: 214 AN: 2112

Alfa AF: 0.0646 Hom.: 589

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
PhyloP100		-3.1
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: rs2319974; hg19: chr18-56416469;