rs2523511

chr6-31539077-C-T

Variant summary

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

The NM_004640.7(DDX39B):c.339+70G>A 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 1,612,668 control chromosomes in the GnomAD database, including 554,719 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 (54736 hom., cov: 31)
  • Exomes 𝑓: 0.83 (499983 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799

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=-0.81).
• 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.339+70G>A		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.1142+70G>A		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.339+70G>A		intron_variant
DDX39B	NR_037852.2	n.397+1245G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.339+70G>A		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128802 AN: 152010 Hom.: 54679 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.860

GnomAD3 exomes AF: 0.856 AC: 211598 AN: 247256 Hom.: 90962 AF XY: 0.861 AC XY: 115833 AN XY: 134582

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.944

Gnomad EAS exome AF: 0.932

Gnomad SAS exome AF: 0.925

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.821

Gnomad OTH exome AF: 0.853

GnomAD4 exome AF: 0.826 AC: 1206696 AN: 1460540 Hom.: 499983 Cov.: 37 AF XY: 0.830 AC XY: 603321 AN XY: 726612

Gnomad4 AFR exome AF: 0.883

Gnomad4 AMR exome AF: 0.865

Gnomad4 ASJ exome AF: 0.940

Gnomad4 EAS exome AF: 0.920

Gnomad4 SAS exome AF: 0.926

Gnomad4 FIN exome AF: 0.816

Gnomad4 NFE exome AF: 0.809

Gnomad4 OTH exome AF: 0.836

GnomAD4 genome AF: 0.847 AC: 128917 AN: 152128 Hom.: 54736 Cov.: 31 AF XY: 0.852 AC XY: 63332 AN XY: 74374

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: 0.813

Gnomad4 OTH AF: 0.861

Alfa AF: 0.833 Hom.: 40556

Bravo AF: 0.851

Asia WGS AF: 0.865 AC: 3011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	9.3
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2523511; hg19: chr6-31506854;