Variant 6-31538967-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000396172.6(DDX39B):c.340-112T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.829 in 1,471,090 control chromosomes in the GnomAD database, including 506,955 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 0.85 ( 54741 hom., cov: 32)

Exomes 𝑓: 0.83 ( 452214 hom. )

Consequence

DDX39B
ENST00000396172.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.115

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 rather VUS (scored 4 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
DDX39B	NM_004640.7 linkuse as main transcript	c.340-112T>G	intron_variant	ENST00000396172.6	NP_004631.1
ATP6V1G2-DDX39B	NR_037853.1 linkuse as main transcript	n.1143-112T>G	intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6 linkuse as main transcript	c.340-112T>G	intron_variant		NP_542165.1
DDX39B	NR_037852.2 linkuse as main transcript	n.397+1355T>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6 linkuse as main transcript	c.340-112T>G		intron_variant		1	NM_004640.7	ENSP00000379475	P1	Q13838-1

Frequencies

GnomAD3 genomes

AF:

0.847

AC:

128820

AN:

152032

Hom.:

54684

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.826

Gnomad AMR

AF:

0.868

Gnomad ASJ

AF:

0.940

Gnomad EAS

AF:

0.925

Gnomad SAS

AF:

0.923

Gnomad FIN

AF:

0.824

Gnomad MID

AF:

0.908

Gnomad NFE

AF:

0.813

Gnomad OTH

AF:

0.860

GnomAD3 exomes

AF:

0.856

AC:

212467

AN:

248342

Hom.:

91288

AF XY:

0.861

AC XY:

115894

AN XY:

134646

show subpopulations

Gnomad AFR exome

AF:

0.873

Gnomad AMR exome

AF:

0.857

Gnomad ASJ exome

AF:

0.944

Gnomad EAS exome

AF:

0.931

Gnomad SAS exome

AF:

0.925

Gnomad FIN exome

AF:

0.816

Gnomad NFE exome

AF:

0.821

Gnomad OTH exome

AF:

0.854

GnomAD4 exome

AF:

0.826

AC:

1090098

AN:

1318940

Hom.:

452214

Cov.:

AF XY:

0.831

AC XY:

551262

AN XY:

663536

show subpopulations

Gnomad4 AFR exome

AF:

0.882

Gnomad4 AMR exome

AF:

0.864

Gnomad4 ASJ exome

AF:

0.940

Gnomad4 EAS exome

AF:

0.921

Gnomad4 SAS exome

AF:

0.926

Gnomad4 FIN exome

AF:

0.816

Gnomad4 NFE exome

AF:

0.808

Gnomad4 OTH exome

AF:

0.835

GnomAD4 genome

AF:

0.847

AC:

128935

AN:

152150

Hom.:

54741

Cov.:

AF XY:

0.852

AC XY:

63325

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.868

Gnomad4 ASJ

AF:

0.940

Gnomad4 EAS

AF:

0.926

Gnomad4 SAS

AF:

0.923

Gnomad4 FIN

AF:

0.824

Gnomad4 NFE

AF:

0.813

Gnomad4 OTH

AF:

0.861

Alfa

AF:

0.830

Hom.:

54425

Bravo

AF:

0.851

Asia WGS

AF:

0.866

AC:

3012

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

DANN

Benign

0.59

BranchPoint Hunter

4.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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