6-31539285-G-C

Position:

• chr6-31539285-G-C

Variant summary

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

The NM_004640.7(DDX39B):​c.212-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,607,168 control chromosomes in the GnomAD database, including 6,754 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 (802 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5952 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Scores: Splicing: ADA: 0.0009793
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899

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: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]

DDX39B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.212-11C>G		intron_variant		ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.212-11C>G		intron_variant			NP_542165.1
DDX39B	NR_037852.2	n.397+1037C>G		intron_variant
ATP6V1G2-DDX39B	NR_037853.1	n.1015-11C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.212-11C>G		intron_variant		1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*426-11C>G		intron_variant		2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12874 AN: 151924 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0915

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0721

GnomAD3 exomes AF: 0.0988 AC: 24112 AN: 244144 Hom.: 1582 AF XY: 0.104 AC XY: 13867 AN XY: 133058

Gnomad AFR exome AF: 0.0471

Gnomad AMR exome AF: 0.0399

Gnomad ASJ exome AF: 0.0944

Gnomad EAS exome AF: 0.127

Gnomad SAS exome AF: 0.162

Gnomad FIN exome AF: 0.219

Gnomad NFE exome AF: 0.0789

Gnomad OTH exome AF: 0.0976

GnomAD4 exome AF: 0.0789 AC: 114781 AN: 1455124 Hom.: 5952 Cov.: 33 AF XY: 0.0823 AC XY: 59501 AN XY: 722622

Gnomad4 AFR exome AF: 0.0482

Gnomad4 AMR exome AF: 0.0426

Gnomad4 ASJ exome AF: 0.0946

Gnomad4 EAS exome AF: 0.155

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.209

Gnomad4 NFE exome AF: 0.0652

Gnomad4 OTH exome AF: 0.0781

GnomAD4 genome AF: 0.0847 AC: 12883 AN: 152044 Hom.: 802 Cov.: 32 AF XY: 0.0949 AC XY: 7055 AN XY: 74330

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.0582

Gnomad4 ASJ AF: 0.0915

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.0748

Gnomad4 OTH AF: 0.0723

Alfa AF: 0.0581 Hom.: 76

Bravo AF: 0.0655

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	-0.83
CADD	Benign	0.36
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00098
dbscSNV1_RF	Benign	0.036
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: rs2071595; hg19: chr6-31507062;