rs2071596

Positions:

• chr6-31538914-G-A
• chr6-31538914-G-C
• chr6-31538914-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.340-59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,563,490 control chromosomes in the GnomAD database, including 27,338 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 0.22 (3928 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23410 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24

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 (MetaRNN=0.0035931468).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.340-59C>T		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.1143-59C>T		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.340-59C>T		intron_variant
DDX39B	NR_037852.2	n.397+1408C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.340-59C>T		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33047 AN: 151862 Hom.: 3929 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.203

GnomAD3 exomes AF: 0.203 AC: 50782 AN: 250300 Hom.: 5729 AF XY: 0.192 AC XY: 26001 AN XY: 135296

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.364

Gnomad SAS exome AF: 0.126

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.175 AC: 246668 AN: 1411508 Hom.: 23410 Cov.: 26 AF XY: 0.171 AC XY: 120885 AN XY: 705202

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.264

Gnomad4 ASJ exome AF: 0.176

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.188

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.186

GnomAD4 genome AF: 0.218 AC: 33077 AN: 151982 Hom.: 3928 Cov.: 32 AF XY: 0.218 AC XY: 16187 AN XY: 74270

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.248

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.361

Gnomad4 SAS AF: 0.128

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.164

Gnomad4 OTH AF: 0.203

Alfa AF: 0.178 Hom.: 5230

Bravo AF: 0.229

TwinsUK AF: 0.174 AC: 647

ALSPAC AF: 0.179 AC: 689

ExAC AF: 0.201 AC: 24352

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.5
DANN	Benign	0.79
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.14	N
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.012
Sift	Benign	0.18	T;D
Sift4G	Uncertain	0.030	D;.
ClinPred		0.00058	T
GERP RS		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2

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: rs2071596; hg19: chr6-31506691; COSMIC: COSV63331076; COSMIC: COSV63331076;