chr6-31537703-A-G

Variant names:

• chr6-31537703-A-G
• rs2734583
• NM_004640.7:c.433-1020T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 62 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=-0.9).
• 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.433-1020T>C		intron	N/A	NP_004631.1
	DDX39B	NM_080598.6		c.433-1020T>C		intron	N/A	NP_542165.1
	DDX39B	NR_037852.2		n.398-1020T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.433-1020T>C		intron	N/A	ENSP00000379475.1
	DDX39B	ENST00000458640.5	TSL:1	c.433-1020T>C		intron	N/A	ENSP00000416269.1
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.*647-1020T>C		intron	N/A	ENSP00000365356.1

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

African (AFR) AF: 0.115 AC: 4776 AN: 41494

American (AMR) AF: 0.0438 AC: 670 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 148 AN: 3460

East Asian (EAS) AF: 0.0627 AC: 324 AN: 5170

South Asian (SAS) AF: 0.0383 AC: 185 AN: 4826

European-Finnish (FIN) AF: 0.0810 AC: 859 AN: 10608

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

European-Non Finnish (NFE) AF: 0.115 AC: 7850 AN: 67980

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

Alfa AF: 0.112 Hom.: 4557

Bravo AF: 0.0978

Asia WGS AF: 0.0520 AC: 182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.54
DANN	Benign	0.62
PhyloP100		-0.47
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: rs2734583; hg19: chr6-31505480;