rs3093978

chr6-31530720-C-A

Variant summary

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

The NM_004640.7(DDX39B):c.1270+59G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,586,998 control chromosomes in the GnomAD database, including 545,605 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 0.85 (54720 hom., cov: 30)
  • Exomes 𝑓: 0.83 (490885 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.413

Genes affected

DDX39B (HGNC:13917): (DExD-box helicase 39B) This gene encodes a member of the DEAD box family of RNA-dependent ATPases that mediate ATP hydrolysis during pre-mRNA splicing. The encoded protein is an essential splicing factor required for association of U2 small nuclear ribonucleoprotein with pre-mRNA, and it also plays an important role in mRNA export from the nucleus to the cytoplasm. This gene belongs to a cluster of genes localized in the vicinity of the genes encoding tumor necrosis factor alpha and tumor necrosis factor beta. These genes are all within the human major histocompatibility complex class III region. Mutations in this gene may be associated with rheumatoid arthritis. Alternative splicing results in multiple transcript variants. Related pseudogenes have been identified on both chromosomes 6 and 11. Read-through transcription also occurs between this gene and the upstream ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) gene. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.1270+59G>T		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.2073+59G>T		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.1270+59G>T		intron_variant
DDX39B	NR_037852.2	n.1235+59G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.1270+59G>T		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128780 AN: 151988 Hom.: 54663 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.812

Gnomad OTH AF: 0.859

GnomAD4 exome AF: 0.826 AC: 1185096 AN: 1434892 Hom.: 490885 Cov.: 32 AF XY: 0.830 AC XY: 590609 AN XY: 711518

Gnomad4 AFR exome AF: 0.885

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.940

Gnomad4 EAS exome AF: 0.921

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.818

Gnomad4 NFE exome AF: 0.808

Gnomad4 OTH exome AF: 0.836

GnomAD4 genome AF: 0.847 AC: 128895 AN: 152106 Hom.: 54720 Cov.: 30 AF XY: 0.852 AC XY: 63332 AN XY: 74372

Gnomad4 AFR AF: 0.876

Gnomad4 AMR AF: 0.868

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.926

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.824

Gnomad4 NFE AF: 0.812

Gnomad4 OTH AF: 0.860

Alfa AF: 0.832 Hom.: 94347

Bravo AF: 0.851

Asia WGS AF: 0.866 AC: 3012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	0.64
Dann	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs3093978; hg19: chr6-31498497;