rs3853601

chr6-31531826-C-G

Variant summary

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

The NM_004640.7(DDX39B):c.868-421G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 172,498 control chromosomes in the GnomAD database, including 1,457 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 0.13 (1328 hom., cov: 31)
  • Exomes 𝑓: 0.090 (129 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.868-421G>C		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.1671-421G>C		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.868-421G>C		intron_variant
DDX39B	NR_037852.2	n.833-421G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.868-421G>C		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19230 AN: 151910 Hom.: 1328 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.0901 AC: 1845 AN: 20470 Hom.: 129 AF XY: 0.0889 AC XY: 968 AN XY: 10890

Gnomad4 AFR exome AF: 0.164

Gnomad4 AMR exome AF: 0.0764

Gnomad4 ASJ exome AF: 0.149

Gnomad4 EAS exome AF: 0.0412

Gnomad4 SAS exome AF: 0.0289

Gnomad4 FIN exome AF: 0.0893

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0916

GnomAD4 genome AF: 0.127 AC: 19241 AN: 152028 Hom.: 1328 Cov.: 31 AF XY: 0.124 AC XY: 9210 AN XY: 74316

Gnomad4 AFR AF: 0.171

Gnomad4 AMR AF: 0.0983

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0194

Gnomad4 SAS AF: 0.0376

Gnomad4 FIN AF: 0.121

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.122

Alfa AF: 0.124 Hom.: 672

Bravo AF: 0.128

Asia WGS AF: 0.0500 AC: 175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.014
Dann	Benign	0.66

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: rs3853601; hg19: chr6-31499603;