rs2523512

Variant names:

• chr6-31539024-G-A
• rs2523512
• NM_004640.7:c.339+123C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31539024-G-A
• chr6-31539024-G-C
• chr6-31539024-G-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.339+123C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,555,856 control chromosomes in the GnomAD database, including 23,220 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 0.16 (2146 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21074 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.249 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.339+123C>T		intron_variant	Intron 3 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.339+123C>T		intron_variant	Intron 3 of 10		NP_542165.1
DDX39B	NR_037852.2	n.397+1298C>T		intron_variant	Intron 2 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1142+123C>T		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.339+123C>T		intron_variant	Intron 3 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*553+123C>T		intron_variant	Intron 5 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25031 AN: 152046 Hom.: 2147 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.196

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.185

GnomAD2 exomes AF: 0.180 AC: 44599 AN: 247838 AF XY: 0.187

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.131

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.165

Gnomad FIN exome AF: 0.192

Gnomad NFE exome AF: 0.178

Gnomad OTH exome AF: 0.180

GnomAD4 exome AF: 0.170 AC: 238585 AN: 1403692 Hom.: 21074 Cov.: 27 AF XY: 0.174 AC XY: 121935 AN XY: 701554

African (AFR) AF: 0.146 AC: 4694 AN: 32210

American (AMR) AF: 0.137 AC: 6103 AN: 44654

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 5112 AN: 25774

East Asian (EAS) AF: 0.157 AC: 6197 AN: 39406

South Asian (SAS) AF: 0.261 AC: 22148 AN: 84908

European-Finnish (FIN) AF: 0.187 AC: 9935 AN: 53248

Middle Eastern (MID) AF: 0.201 AC: 1136 AN: 5652

European-Non Finnish (NFE) AF: 0.163 AC: 172898 AN: 1059428

Other (OTH) AF: 0.177 AC: 10362 AN: 58412

GnomAD4 genome AF: 0.165 AC: 25048 AN: 152164 Hom.: 2146 Cov.: 33 AF XY: 0.165 AC XY: 12304 AN XY: 74362

African (AFR) AF: 0.143 AC: 5948 AN: 41508

American (AMR) AF: 0.154 AC: 2349 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.196 AC: 679 AN: 3472

East Asian (EAS) AF: 0.163 AC: 845 AN: 5184

South Asian (SAS) AF: 0.261 AC: 1256 AN: 4820

European-Finnish (FIN) AF: 0.181 AC: 1910 AN: 10570

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11544 AN: 67992

Other (OTH) AF: 0.186 AC: 393 AN: 2116

Alfa AF: 0.173 Hom.: 8814

Bravo AF: 0.162

Asia WGS AF: 0.237 AC: 823 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	8.1
DANN	Benign	0.81
PhyloP100		-0.088
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: rs2523512; hg19: chr6-31506801;