NM_004640.7:c.340-16C>A

Variant names:

• chr6-31538871-G-T
• rs933208
• NM_004640.7:c.340-16C>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.340-16C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 1,610,388 control chromosomes in the GnomAD database, including 453,136 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 0.76 (44577 hom., cov: 32)
  • Exomes 𝑓: 0.75 (408559 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 25 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 (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004640.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	NM_004640.7	MANE Select	c.340-16C>A		intron	N/A	NP_004631.1
	DDX39B	NM_080598.6		c.340-16C>A		intron	N/A	NP_542165.1
	DDX39B	NR_037852.2		n.397+1451C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.340-16C>A		intron	N/A	ENSP00000379475.1
	DDX39B	ENST00000458640.5	TSL:1	c.340-16C>A		intron	N/A	ENSP00000416269.1
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.*554-16C>A		intron	N/A	ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.762 AC: 115839 AN: 151922 Hom.: 44530 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.780

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.586

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.789

GnomAD2 exomes AF: 0.758 AC: 190486 AN: 251372 AF XY: 0.757

Gnomad AFR exome AF: 0.826

Gnomad AMR exome AF: 0.818

Gnomad ASJ exome AF: 0.851

Gnomad EAS exome AF: 0.804

Gnomad FIN exome AF: 0.598

Gnomad NFE exome AF: 0.743

Gnomad OTH exome AF: 0.757

GnomAD4 exome AF: 0.747 AC: 1089622 AN: 1458348 Hom.: 408559 Cov.: 39 AF XY: 0.748 AC XY: 542629 AN XY: 725660

African (AFR) AF: 0.836 AC: 27893 AN: 33378

American (AMR) AF: 0.822 AC: 36769 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 22074 AN: 26110

East Asian (EAS) AF: 0.766 AC: 30382 AN: 39678

South Asian (SAS) AF: 0.763 AC: 65701 AN: 86158

European-Finnish (FIN) AF: 0.607 AC: 32407 AN: 53400

Middle Eastern (MID) AF: 0.778 AC: 4482 AN: 5758

European-Non Finnish (NFE) AF: 0.743 AC: 824232 AN: 1108870

Other (OTH) AF: 0.758 AC: 45682 AN: 60288

GnomAD4 genome AF: 0.763 AC: 115945 AN: 152040 Hom.: 44577 Cov.: 32 AF XY: 0.757 AC XY: 56225 AN XY: 74314

African (AFR) AF: 0.824 AC: 34152 AN: 41446

American (AMR) AF: 0.810 AC: 12371 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2947 AN: 3472

East Asian (EAS) AF: 0.781 AC: 4053 AN: 5188

South Asian (SAS) AF: 0.737 AC: 3550 AN: 4818

European-Finnish (FIN) AF: 0.586 AC: 6182 AN: 10550

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.738 AC: 50154 AN: 67986

Other (OTH) AF: 0.789 AC: 1664 AN: 2108

Alfa AF: 0.761 Hom.: 64350

Bravo AF: 0.785

Asia WGS AF: 0.744 AC: 2588 AN: 3478

EpiCase AF: 0.756

EpiControl AF: 0.766

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.2
DANN	Benign	0.83
PhyloP100		-0.16
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs933208; hg19: chr6-31506648; COSMIC: COSV63331073; COSMIC: COSV63331073;