rs2239709

Positions:

• chr6-31539670-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004640.7(DDX39B):​c.212-396G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 152,200 control chromosomes in the GnomAD database, including 798 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 0.085 (798 hom., cov: 32)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213

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 (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.212-396G>A		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.1015-396G>A		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.212-396G>A		intron_variant
DDX39B	NR_037852.2	n.397+652G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.212-396G>A		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12864 AN: 152080 Hom.: 798 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0582

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0721

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0846 AC: 12873 AN: 152200 Hom.: 798 Cov.: 32 AF XY: 0.0947 AC XY: 7049 AN XY: 74402

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.0581

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.143

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0760 Hom.: 696

Bravo AF: 0.0654

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	11
DANN	Benign	0.50

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: rs2239709; hg19: chr6-31507447;