rs2734583

chr6-31537703-A-G

Variant summary

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

The NM_004640.7(DDX39B):c.433-1020T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 152,138 control chromosomes in the GnomAD database, including 864 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 0.099 (864 hom., cov: 32)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.469

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX39B	NM_004640.7	c.433-1020T>C		intron_variant		ENST00000396172.6
ATP6V1G2-DDX39B	NR_037853.1	n.1236-1020T>C		intron_variant, non_coding_transcript_variant
DDX39B	NM_080598.6	c.433-1020T>C		intron_variant
DDX39B	NR_037852.2	n.398-1020T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX39B	ENST00000396172.6	c.433-1020T>C		intron_variant		1	NM_004640.7	P1

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15117 AN: 152020 Hom.: 862 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0428

Gnomad EAS AF: 0.0625

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0810

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0724

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0994 AC: 15123 AN: 152138 Hom.: 864 Cov.: 32 AF XY: 0.0947 AC XY: 7044 AN XY: 74374

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0428

Gnomad4 EAS AF: 0.0627

Gnomad4 SAS AF: 0.0383

Gnomad4 FIN AF: 0.0810

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.107 Hom.: 1422

Bravo AF: 0.0978

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.54
Dann	Benign	0.62

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: rs2734583; hg19: chr6-31505480;