rs2523511

Variant names:

• chr6-31539077-C-T
• rs2523511
• NM_004640.7:c.339+70G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004640.7(DDX39B):​c.339+70G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 1,612,668 control chromosomes in the GnomAD database, including 554,719 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 0.85 (54736 hom., cov: 31)
  • Exomes 𝑓: 0.83 (499983 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.799
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.339+70G>A		intron_variant	Intron 3 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.339+70G>A		intron_variant	Intron 3 of 10		NP_542165.1
DDX39B	NR_037852.2	n.397+1245G>A		intron_variant	Intron 2 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1142+70G>A		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.339+70G>A		intron_variant	Intron 3 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*553+70G>A		intron_variant	Intron 5 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128802 AN: 152010 Hom.: 54679 Cov.: 31

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.926

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.860

GnomAD2 exomes AF: 0.856 AC: 211598 AN: 247256 AF XY: 0.861

Gnomad AFR exome AF: 0.873

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.944

Gnomad EAS exome AF: 0.932

Gnomad FIN exome AF: 0.817

Gnomad NFE exome AF: 0.821

Gnomad OTH exome AF: 0.853

GnomAD4 exome AF: 0.826 AC: 1206696 AN: 1460540 Hom.: 499983 Cov.: 37 AF XY: 0.830 AC XY: 603321 AN XY: 726612

African (AFR) AF: 0.883 AC: 29561 AN: 33462

American (AMR) AF: 0.865 AC: 38676 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 24557 AN: 26126

East Asian (EAS) AF: 0.920 AC: 36539 AN: 39696

South Asian (SAS) AF: 0.926 AC: 79870 AN: 86244

European-Finnish (FIN) AF: 0.816 AC: 43343 AN: 53096

Middle Eastern (MID) AF: 0.913 AC: 5265 AN: 5768

European-Non Finnish (NFE) AF: 0.809 AC: 898452 AN: 1111080

Other (OTH) AF: 0.836 AC: 50433 AN: 60344

GnomAD4 genome AF: 0.847 AC: 128917 AN: 152128 Hom.: 54736 Cov.: 31 AF XY: 0.852 AC XY: 63332 AN XY: 74374

African (AFR) AF: 0.876 AC: 36339 AN: 41486

American (AMR) AF: 0.868 AC: 13271 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.940 AC: 3264 AN: 3472

East Asian (EAS) AF: 0.926 AC: 4800 AN: 5184

South Asian (SAS) AF: 0.923 AC: 4452 AN: 4822

European-Finnish (FIN) AF: 0.824 AC: 8726 AN: 10594

Middle Eastern (MID) AF: 0.904 AC: 264 AN: 292

European-Non Finnish (NFE) AF: 0.813 AC: 55227 AN: 67968

Other (OTH) AF: 0.861 AC: 1822 AN: 2116

Alfa AF: 0.833 Hom.: 75385

Bravo AF: 0.851

Asia WGS AF: 0.865 AC: 3011 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.3
DANN	Benign	0.57
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2523511; hg19: chr6-31506854;