rs2523505

Positions:

• chr6-31542225-C-G

Variant summary

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

The ENST00000458640.5(DDX39B):​c.-278G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.063 in 666,924 control chromosomes in the GnomAD database, including 1,647 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 0.075 (449 hom., cov: 33)
  • Exomes 𝑓: 0.060 (1198 hom.)
• Consequence: DDX39B ENST00000458640.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.725

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]

ATP6V1G2-DDX39B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATP6V1G2-DDX39B	NR_037853.1	n.473-77G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATP6V1G2-DDX39B	ENST00000376185.5	n.184-77G>C		intron_variant		2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.0753 AC: 10819 AN: 143718 Hom.: 451 Cov.: 33

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0806

Gnomad ASJ AF: 0.0672

Gnomad EAS AF: 0.0228

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0365

Gnomad MID AF: 0.0516

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.0813

GnomAD4 exome AF: 0.0597 AC: 31212 AN: 523086 Hom.: 1198 Cov.: 0 AF XY: 0.0569 AC XY: 15905 AN XY: 279288

Gnomad4 AFR exome AF: 0.0900

Gnomad4 AMR exome AF: 0.0656

Gnomad4 ASJ exome AF: 0.0617

Gnomad4 EAS exome AF: 0.0101

Gnomad4 SAS exome AF: 0.0204

Gnomad4 FIN exome AF: 0.0344

Gnomad4 NFE exome AF: 0.0736

Gnomad4 OTH exome AF: 0.0612

GnomAD4 genome AF: 0.0752 AC: 10812 AN: 143838 Hom.: 449 Cov.: 33 AF XY: 0.0721 AC XY: 5081 AN XY: 70474

Gnomad4 AFR AF: 0.0918

Gnomad4 AMR AF: 0.0804

Gnomad4 ASJ AF: 0.0672

Gnomad4 EAS AF: 0.0229

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.0365

Gnomad4 NFE AF: 0.0788

Gnomad4 OTH AF: 0.0794

Alfa AF: 0.0724 Hom.: 57

Bravo AF: 0.0789

Asia WGS AF: 0.0210 AC: 73 AN: 3460

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.7
DANN	Benign	0.39

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: rs2523505; hg19: chr6-31510002;