rs9281523

Variant names:

• chr6-31530467-G-GC
• rs9281523
• NM_004640.7:c.1271-18dupG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004640.7(DDX39B):​c.1271-18dupG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 1,612,418 control chromosomes in the GnomAD database, including 11,986 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.099 (857 hom., cov: 29)
  • Exomes 𝑓: 0.11 (11129 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.396
• Publications: 5 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]

MCCD1 (HGNC:20668): (mitochondrial coiled-coil domain 1) Predicted to be located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.113 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.1271-18dupG		intron	N/A	NP_004631.1
	DDX39B	NM_080598.6		c.1271-18dupG		intron	N/A	NP_542165.1
	DDX39B	NR_037852.2		n.1236-18dupG		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.1271-18dupG		intron	N/A	ENSP00000379475.1
	DDX39B	ENST00000458640.5	TSL:1	c.1271-18dupG		intron	N/A	ENSP00000416269.1
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.*1485-18dupG		intron	N/A	ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.0994 AC: 15107 AN: 151992 Hom.: 855 Cov.: 29

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0429

Gnomad EAS AF: 0.0629

Gnomad SAS AF: 0.0377

Gnomad FIN AF: 0.0811

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.0724

GnomAD2 exomes AF: 0.0813 AC: 20014 AN: 246126 AF XY: 0.0800

Gnomad AFR exome AF: 0.114

Gnomad AMR exome AF: 0.0298

Gnomad ASJ exome AF: 0.0401

Gnomad EAS exome AF: 0.0887

Gnomad FIN exome AF: 0.0792

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.0723

GnomAD4 exome AF: 0.114 AC: 166961 AN: 1460308 Hom.: 11129 Cov.: 33 AF XY: 0.112 AC XY: 81109 AN XY: 726490

African (AFR) AF: 0.115 AC: 3845 AN: 33468

American (AMR) AF: 0.0318 AC: 1420 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.0436 AC: 1139 AN: 26132

East Asian (EAS) AF: 0.0404 AC: 1604 AN: 39700

South Asian (SAS) AF: 0.0416 AC: 3591 AN: 86230

European-Finnish (FIN) AF: 0.0834 AC: 4364 AN: 52306

Middle Eastern (MID) AF: 0.0210 AC: 121 AN: 5764

European-Non Finnish (NFE) AF: 0.130 AC: 144567 AN: 1111636

Other (OTH) AF: 0.105 AC: 6310 AN: 60364

GnomAD4 genome AF: 0.0994 AC: 15113 AN: 152110 Hom.: 857 Cov.: 29 AF XY: 0.0947 AC XY: 7042 AN XY: 74374

African (AFR) AF: 0.115 AC: 4779 AN: 41476

American (AMR) AF: 0.0436 AC: 666 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0429 AC: 149 AN: 3470

East Asian (EAS) AF: 0.0630 AC: 326 AN: 5172

South Asian (SAS) AF: 0.0379 AC: 183 AN: 4826

European-Finnish (FIN) AF: 0.0811 AC: 859 AN: 10592

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7839 AN: 67978

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.101 Hom.: 212

Bravo AF: 0.0979

Asia WGS AF: 0.0520 AC: 180 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.40
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: rs9281523; hg19: chr6-31498244;