rs3130059

Positions:

• chr6-31541507-G-C
• chr6-31541507-G-T

Variant summary

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

The NM_004640.7(DDX39B):​c.-133+443C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 390,888 control chromosomes in the GnomAD database, including 25,607 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 0.38 (11611 hom., cov: 31)
  • Exomes 𝑓: 0.33 (13996 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.-133+443C>G		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.671+443C>G		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.-3+443C>G		intron_variant
DDX39B	NR_037852.2	n.54+443C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.-133+443C>G		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58150 AN: 151694 Hom.: 11599 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.334 AC: 79829 AN: 239076 Hom.: 13996 Cov.: 0 AF XY: 0.328 AC XY: 43696 AN XY: 133306

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.336

Gnomad4 ASJ exome AF: 0.260

Gnomad4 EAS exome AF: 0.499

Gnomad4 SAS exome AF: 0.286

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.338

GnomAD4 genome AF: 0.383 AC: 58201 AN: 151812 Hom.: 11611 Cov.: 31 AF XY: 0.379 AC XY: 28137 AN XY: 74198

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.303

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.354

Alfa AF: 0.350 Hom.: 5312

Bravo AF: 0.392

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.52

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: rs3130059; hg19: chr6-31509284;