dbSNP rs2239528: DDX39B:c.-381T>G (chr6-31542328-A-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000458640.5(DDX39B):c.-381T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00128 in 684,218 control chromosomes in the GnomAD database, including 13 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 0.00039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 13 hom. )

Consequence

DDX39B
ENST00000458640.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.464

Publications

40 publications found

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-AS1 (HGNC:39771): (DDX39B antisense RNA 1)

DDX39B-AS1 links:

ENSG00000299760 (HGNC:):

ENSG00000299760 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.105).

BS2

High AC in GnomAd4 at 60 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
DDX39B-AS1	NR_133674.1 link	n.25A>C	non_coding_transcript_exon_variant	Exon 1 of 2
DDX39B-AS1	NR_133675.1 link	n.25A>C	non_coding_transcript_exon_variant	Exon 1 of 2
ATP6V1G2-DDX39B	NR_037853.1 link	n.473-180T>G	intron_variant	Intron 2 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2-DDX39B	ENST00000376185.5 link	n.184-180T>G		intron_variant	Intron 2 of 12	2		ENSP00000365356.1		F2Z307

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00201

AC:

275

AN:

136984

AF XY:

0.00265

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000181

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.00153

AC:

814

AN:

532044

Hom.:

Cov.:

AF XY:

0.00222

AC XY:

642

AN XY:

288650

show subpopulations

African (AFR)

AF:

0.000130

AC:

AN:

15438

American (AMR)

AF:

0.00

AC:

AN:

34078

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19588

East Asian (EAS)

AF:

0.00

AC:

AN:

30920

South Asian (SAS)

AF:

0.0123

AC:

760

AN:

61754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31172

Middle Eastern (MID)

AF:

0.00125

AC:

AN:

3994

European-Non Finnish (NFE)

AF:

0.0000622

AC:

AN:

305598

Other (OTH)

AF:

0.000949

AC:

AN:

29502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

112

167

223

279

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000394

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41522

American (AMR)

AF:

0.00

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5170

South Asian (SAS)

AF:

0.0118

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67998

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00000350

Hom.:

165358

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.8

(source)

DANN

Benign

0.78

PhyloP100

-0.46

PromoterAI

0.027

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over