rs2239527

chr6-31542002-C-Gchr6-31542002-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4 BA1

The NM_004640.7(DDX39B):c.-185G>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 0.336 in 679,910 control chromosomes in the GnomAD database, including 40,492 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 0.37 (11097 hom., cov: 33)
  • Exomes 𝑓: 0.32 (29395 hom.)
• Consequence: DDX39B NM_004640.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.15).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.-185G>C		5_prime_UTR_variant	1/11	ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.619G>C		non_coding_transcript_exon_variant	3/13
DDX39B	NM_080598.6	c.-55G>C		5_prime_UTR_variant	1/11
DDX39B	NR_037852.2	n.2G>C		non_coding_transcript_exon_variant	1/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.-185G>C		5_prime_UTR_variant	1/11	1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56889 AN: 152014 Hom.: 11087 Cov.: 33

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.302

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.341

GnomAD3 exomes AF: 0.328 AC: 43943 AN: 133932 Hom.: 7781 AF XY: 0.318 AC XY: 23166 AN XY: 72822

Gnomad AFR exome AF: 0.490

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.252

Gnomad EAS exome AF: 0.503

Gnomad SAS exome AF: 0.206

Gnomad FIN exome AF: 0.304

Gnomad NFE exome AF: 0.336

Gnomad OTH exome AF: 0.333

GnomAD4 exome AF: 0.324 AC: 171224 AN: 527778 Hom.: 29395 Cov.: 0 AF XY: 0.315 AC XY: 88690 AN XY: 281824

Gnomad4 AFR exome AF: 0.488

Gnomad4 AMR exome AF: 0.331

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.422

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.334

Gnomad4 OTH exome AF: 0.340

GnomAD4 genome AF: 0.374 AC: 56931 AN: 152132 Hom.: 11097 Cov.: 33 AF XY: 0.369 AC XY: 27471 AN XY: 74390

Gnomad4 AFR AF: 0.487

Gnomad4 AMR AF: 0.340

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.214

Gnomad4 FIN AF: 0.302

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.339

Alfa AF: 0.267 Hom.: 1051

Bravo AF: 0.383

Asia WGS AF: 0.311 AC: 1084 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.15
Cadd	Benign	20
Dann	Benign	0.94

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: rs2239527; hg19: chr6-31509779; COSMIC: COSV58214051; COSMIC: COSV58214051;