rs3093976

Variant names:

• chr6-31535084-A-G
• rs3093976
• NM_004640.7:c.735+283T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31535084-A-G
• chr6-31535084-A-T

Variant summary

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

The NM_004640.7(DDX39B):​c.735+283T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 476,068 control chromosomes in the GnomAD database, including 171,753 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 (54704 hom., cov: 30)
  • Exomes 𝑓: 0.85 (117049 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.555
• 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=-0.76).
• 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.735+283T>C		intron_variant	Intron 6 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.735+283T>C		intron_variant	Intron 6 of 10		NP_542165.1
DDX39B	NR_037852.2	n.700+283T>C		intron_variant	Intron 4 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1538+283T>C		intron_variant	Intron 8 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.735+283T>C		intron_variant	Intron 6 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*949+283T>C		intron_variant	Intron 8 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128720 AN: 151892 Hom.: 54647 Cov.: 30

Gnomad AFR AF: 0.876

Gnomad AMI AF: 0.827

Gnomad AMR AF: 0.868

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.825

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.813

Gnomad OTH AF: 0.859

GnomAD4 exome AF: 0.847 AC: 274617 AN: 324058 Hom.: 117049 Cov.: 2 AF XY: 0.854 AC XY: 145757 AN XY: 170700

African (AFR) AF: 0.881 AC: 8749 AN: 9934

American (AMR) AF: 0.867 AC: 12599 AN: 14530

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 9589 AN: 10218

East Asian (EAS) AF: 0.922 AC: 19923 AN: 21614

South Asian (SAS) AF: 0.928 AC: 36049 AN: 38832

European-Finnish (FIN) AF: 0.823 AC: 14255 AN: 17322

Middle Eastern (MID) AF: 0.921 AC: 1299 AN: 1410

European-Non Finnish (NFE) AF: 0.817 AC: 156223 AN: 191316

Other (OTH) AF: 0.844 AC: 15931 AN: 18882

GnomAD4 genome AF: 0.848 AC: 128835 AN: 152010 Hom.: 54704 Cov.: 30 AF XY: 0.852 AC XY: 63277 AN XY: 74286

African (AFR) AF: 0.876 AC: 36312 AN: 41440

American (AMR) AF: 0.868 AC: 13261 AN: 15274

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

East Asian (EAS) AF: 0.926 AC: 4785 AN: 5168

South Asian (SAS) AF: 0.923 AC: 4450 AN: 4822

European-Finnish (FIN) AF: 0.825 AC: 8710 AN: 10562

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.813 AC: 55223 AN: 67962

Other (OTH) AF: 0.860 AC: 1810 AN: 2104

Alfa AF: 0.831 Hom.: 134393

Bravo AF: 0.851

Asia WGS AF: 0.866 AC: 3012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	13
DANN	Benign	0.60
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3093976; hg19: chr6-31502861;