Variant rs2516478 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.1123-34C>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 1,613,492 control chromosomes in the GnomAD database, including 23,752 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.16 ( 2114 hom., cov: 31)

Exomes 𝑓: 0.17 ( 21638 hom. )

Consequence

DDX39B
NM_004640.7 intron

Scores

Splicing: ADA: 0.00006553

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.30

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:):

ATP6V1G2-DDX39B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
DDX39B	NM_004640.7 linkuse as main transcript	c.1123-34C>T	intron_variant	ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1 linkuse as main transcript	n.1926-34C>T	intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6 linkuse as main transcript	c.1123-34C>T	intron_variant
DDX39B	NR_037852.2 linkuse as main transcript	n.1088-34C>T	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6 linkuse as main transcript	c.1123-34C>T		intron_variant		1	NM_004640.7	P1	Q13838-1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24901

AN:

151968

Hom.:

2115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.194

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.179

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.169

Gnomad OTH

AF:

0.184

GnomAD3 exomes

AF:

0.179

AC:

44870

AN:

250890

Hom.:

4229

AF XY:

0.186

AC XY:

25194

AN XY:

135644

show subpopulations

Gnomad AFR exome

AF:

0.147

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.200

Gnomad EAS exome

AF:

0.164

Gnomad SAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.189

Gnomad NFE exome

AF:

0.177

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.169

AC:

247104

AN:

1461406

Hom.:

21638

Cov.:

AF XY:

0.173

AC XY:

125701

AN XY:

726900

show subpopulations

Gnomad4 AFR exome

AF:

0.145

Gnomad4 AMR exome

AF:

0.137

Gnomad4 ASJ exome

AF:

0.198

Gnomad4 EAS exome

AF:

0.157

Gnomad4 SAS exome

AF:

0.260

Gnomad4 FIN exome

AF:

0.184

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.164

AC:

24918

AN:

152086

Hom.:

2114

Cov.:

AF XY:

0.165

AC XY:

12243

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.143

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.194

Gnomad4 EAS

AF:

0.163

Gnomad4 SAS

AF:

0.260

Gnomad4 FIN

AF:

0.179

Gnomad4 NFE

AF:

0.169

Gnomad4 OTH

AF:

0.184

Alfa

AF:

0.160

Hom.:

1696

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

-0.84

CADD

Benign

0.41

DANN

Benign

0.53

BranchPoint Hunter

1.0

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000066

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.10

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