rs2523512

chr6-31539024-G-A

Variant summary

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

The NM_004640.7(DDX39B):c.339+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,555,856 control chromosomes in the GnomAD database, including 23,220 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 0.16 (2146 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21074 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.339+123C>T		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.1142+123C>T		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.339+123C>T		intron_variant
DDX39B	NR_037852.2	n.397+1298C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.339+123C>T		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25031 AN: 152046 Hom.: 2147 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.185

GnomAD3 exomes AF: 0.180 AC: 44599 AN: 247838 Hom.: 4235 AF XY: 0.187 AC XY: 25136 AN XY: 134570

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.165

Gnomad SAS exome AF: 0.255

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.170 AC: 238585 AN: 1403692 Hom.: 21074 Cov.: 27 AF XY: 0.174 AC XY: 121935 AN XY: 701554

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.177

GnomAD4 genome AF: 0.165 AC: 25048 AN: 152164 Hom.: 2146 Cov.: 33 AF XY: 0.165 AC XY: 12304 AN XY: 74362

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.196

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.261

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.186

Alfa AF: 0.173 Hom.: 3638

Bravo AF: 0.162

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
Cadd	Benign	8.1
Dann	Benign	0.81

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: rs2523512; hg19: chr6-31506801;