rs2523506

chr6-31542190-G-T

Variant summary

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

The ENST00000458640.5(DDX39B):c.-243C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 680,392 control chromosomes in the GnomAD database, including 9,759 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 0.15 (1778 hom., cov: 34)
  • Exomes 𝑓: 0.17 (7981 hom.)
• Consequence: DDX39B ENST00000458640.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

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=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP6V1G2-DDX39B	NR_037853.1	n.473-42C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000458640.5	c.-243C>A		5_prime_UTR_variant	1/11	1		P1
DDX39B	ENST00000482195.5	n.212C>A		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22642 AN: 152062 Hom.: 1780 Cov.: 34

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.164

GnomAD3 exomes AF: 0.169 AC: 22475 AN: 133352 Hom.: 2041 AF XY: 0.176 AC XY: 12777 AN XY: 72524

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.164

Gnomad SAS exome AF: 0.246

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.169 AC: 89289 AN: 528212 Hom.: 7981 Cov.: 0 AF XY: 0.174 AC XY: 49232 AN XY: 282220

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.252

Gnomad4 FIN exome AF: 0.187

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.149 AC: 22653 AN: 152180 Hom.: 1778 Cov.: 34 AF XY: 0.150 AC XY: 11197 AN XY: 74410

Gnomad4 AFR AF: 0.119

Gnomad4 AMR AF: 0.136

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.249

Gnomad4 FIN AF: 0.180

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.165

Alfa AF: 0.158 Hom.: 1563

Bravo AF: 0.144

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	5.3
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2523506; hg19: chr6-31509967; COSMIC: COSV58214333; COSMIC: COSV58214333;