Variant rs933208 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004640.7(DDX39B):c.340-16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,610,388 control chromosomes in the GnomAD database, including 453,136 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 0.76 ( 44577 hom., cov: 32)

Exomes 𝑓: 0.75 ( 408559 hom. )

Consequence

DDX39B
NM_004640.7 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.156

Variant links:

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]

DDX39B links:

ATP6V1G2-DDX39B (HGNC:41999): (ATP6V1G2-DDX39B readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring ATP6V1G2 (ATPase, H+ transporting, lysosomal 13kDa, V1 subunit G2) and DDX39B (DEAD box polypeptide 39B) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript and is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

ATP6V1G2-DDX39B links:

DDX39B (HGNC:):

DDX39B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.76).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
DDX39B	NM_004640.7 linkuse as main transcript	c.340-16C>A	intron_variant	ENST00000396172.6	NP_004631.1	Q13838-1A0A024RCM3
DDX39B	NM_080598.6 linkuse as main transcript	c.340-16C>A	intron_variant		NP_542165.1	Q13838-1A0A024RCM3
DDX39B	NR_037852.2 linkuse as main transcript	n.397+1451C>A	intron_variant
ATP6V1G2-DDX39B	NR_037853.1 linkuse as main transcript	n.1143-16C>A	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6 linkuse as main transcript	c.340-16C>A		intron_variant		1	NM_004640.7	ENSP00000379475.1		Q13838-1
ATP6V1G2-DDX39B	ENST00000376185.5 linkuse as main transcript	n.*554-16C>A		intron_variant		2		ENSP00000365356.1		F2Z307

Frequencies

GnomAD3 genomes

AF:

0.762

AC:

115839

AN:

151922

Hom.:

44530

Cov.:

show subpopulations

Gnomad AFR

AF:

0.824

Gnomad AMI

AF:

0.697

Gnomad AMR

AF:

0.810

Gnomad ASJ

AF:

0.849

Gnomad EAS

AF:

0.780

Gnomad SAS

AF:

0.738

Gnomad FIN

AF:

0.586

Gnomad MID

AF:

0.825

Gnomad NFE

AF:

0.738

Gnomad OTH

AF:

0.789

GnomAD3 exomes

AF:

0.758

AC:

190486

AN:

251372

Hom.:

72778

AF XY:

0.757

AC XY:

102874

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.826

Gnomad AMR exome

AF:

0.818

Gnomad ASJ exome

AF:

0.851

Gnomad EAS exome

AF:

0.804

Gnomad SAS exome

AF:

0.764

Gnomad FIN exome

AF:

0.598

Gnomad NFE exome

AF:

0.743

Gnomad OTH exome

AF:

0.757

GnomAD4 exome

AF:

0.747

AC:

1089622

AN:

1458348

Hom.:

408559

Cov.:

AF XY:

0.748

AC XY:

542629

AN XY:

725660

show subpopulations

Gnomad4 AFR exome

AF:

0.836

Gnomad4 AMR exome

AF:

0.822

Gnomad4 ASJ exome

AF:

0.845

Gnomad4 EAS exome

AF:

0.766

Gnomad4 SAS exome

AF:

0.763

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.743

Gnomad4 OTH exome

AF:

0.758

GnomAD4 genome

AF:

0.763

AC:

115945

AN:

152040

Hom.:

44577

Cov.:

AF XY:

0.757

AC XY:

56225

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.824

Gnomad4 AMR

AF:

0.810

Gnomad4 ASJ

AF:

0.849

Gnomad4 EAS

AF:

0.781

Gnomad4 SAS

AF:

0.737

Gnomad4 FIN

AF:

0.586

Gnomad4 NFE

AF:

0.738

Gnomad4 OTH

AF:

0.789

Alfa

AF:

0.759

Hom.:

43784

Bravo

AF:

0.785

Asia WGS

AF:

0.744

AC:

2588

AN:

3478

EpiCase

AF:

0.756

EpiControl

AF:

0.766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

7.2

DANN

Benign

0.83

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over