ENST00000458640.5:c.-243C>A

Variant names:

• chr6-31542190-G-T
• rs2523506
• ENST00000458640.5:c.-243C>A

Variant summary

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

The ENST00000458640.5(DDX39B):​c.-243C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 680,392 control chromosomes in the GnomAD database, including 9,759 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 0.15 (1778 hom., cov: 34)
  • Exomes 𝑓: 0.17 (7981 hom.)
• Consequence: DDX39B ENST00000458640.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203
• Publications: 26 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]

ENSG00000299760 (HGNC:):

DDX39B-AS1 (HGNC:39771): (DDX39B antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000458640.5. 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
	ATP6V1G2-DDX39B	NR_037853.1		n.473-42C>A		intron	N/A
	DDX39B	NM_004640.7	MANE Select	c.-373C>A		upstream_gene	N/A	NP_004631.1
	DDX39B	NM_080598.6		c.-243C>A		upstream_gene	N/A	NP_542165.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	ENST00000458640.5	TSL:1	c.-243C>A		5_prime_UTR	Exon 1 of 11	ENSP00000416269.1
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.184-42C>A		intron	N/A	ENSP00000365356.1
	DDX39B	ENST00000482195.5	TSL:2	n.212C>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22642 AN: 152062 Hom.: 1780 Cov.: 34

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.164

GnomAD2 exomes AF: 0.169 AC: 22475 AN: 133352 AF XY: 0.176

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.124

Gnomad ASJ exome AF: 0.158

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.190

Gnomad NFE exome AF: 0.163

Gnomad OTH exome AF: 0.163

GnomAD4 exome AF: 0.169 AC: 89289 AN: 528212 Hom.: 7981 Cov.: 0 AF XY: 0.174 AC XY: 49232 AN XY: 282220

African (AFR) AF: 0.125 AC: 1895 AN: 15144

American (AMR) AF: 0.128 AC: 4265 AN: 33436

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 2950 AN: 19672

East Asian (EAS) AF: 0.157 AC: 4929 AN: 31480

South Asian (SAS) AF: 0.252 AC: 15634 AN: 62008

European-Finnish (FIN) AF: 0.187 AC: 6244 AN: 33386

Middle Eastern (MID) AF: 0.151 AC: 604 AN: 4006

European-Non Finnish (NFE) AF: 0.160 AC: 47905 AN: 299630

Other (OTH) AF: 0.165 AC: 4863 AN: 29450

GnomAD4 genome AF: 0.149 AC: 22653 AN: 152180 Hom.: 1778 Cov.: 34 AF XY: 0.150 AC XY: 11197 AN XY: 74410

African (AFR) AF: 0.119 AC: 4937 AN: 41528

American (AMR) AF: 0.136 AC: 2086 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3472

East Asian (EAS) AF: 0.162 AC: 839 AN: 5180

South Asian (SAS) AF: 0.249 AC: 1202 AN: 4828

European-Finnish (FIN) AF: 0.180 AC: 1901 AN: 10580

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10755 AN: 67984

Other (OTH) AF: 0.165 AC: 347 AN: 2108

Alfa AF: 0.156 Hom.: 2386

Bravo AF: 0.144

Asia WGS AF: 0.223 AC: 776 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	5.3
DANN	Benign	0.69
PhyloP100		-0.20
PromoterAI		0.040	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs2523506; hg19: chr6-31509967; COSMIC: COSV58214333; COSMIC: COSV58214333;