rs2516478

Variant names:

• chr6-31530960-G-A
• rs2516478
• NM_004640.7:c.1123-34C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31530960-G-A
• chr6-31530960-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004640.7(DDX39B):​c.1123-34C>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 1,613,492 control chromosomes in the GnomAD database, including 23,752 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.16 (2114 hom., cov: 31)
  • Exomes 𝑓: 0.17 (21638 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Scores: Splicing: ADA: 0.00006553
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.30

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 1 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.1123-34C>T		intron_variant	Intron 9 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.1123-34C>T		intron_variant	Intron 9 of 10		NP_542165.1
DDX39B	NR_037852.2	n.1088-34C>T		intron_variant	Intron 7 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1926-34C>T		intron_variant	Intron 11 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.1123-34C>T		intron_variant	Intron 9 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*1337-34C>T		intron_variant	Intron 11 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24901 AN: 151968 Hom.: 2115 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.0582

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.179

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.169

Gnomad OTH AF: 0.184

GnomAD3 exomes AF: 0.179 AC: 44870 AN: 250890 Hom.: 4229 AF XY: 0.186 AC XY: 25194 AN XY: 135644

Gnomad AFR exome AF: 0.147

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.200

Gnomad EAS exome AF: 0.164

Gnomad SAS exome AF: 0.254

Gnomad FIN exome AF: 0.189

Gnomad NFE exome AF: 0.177

Gnomad OTH exome AF: 0.179

GnomAD4 exome AF: 0.169 AC: 247104 AN: 1461406 Hom.: 21638 Cov.: 38 AF XY: 0.173 AC XY: 125701 AN XY: 726900

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.198

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.260

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.163

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.164 AC: 24918 AN: 152086 Hom.: 2114 Cov.: 31 AF XY: 0.165 AC XY: 12243 AN XY: 74342

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.163

Gnomad4 SAS AF: 0.260

Gnomad4 FIN AF: 0.179

Gnomad4 NFE AF: 0.169

Gnomad4 OTH AF: 0.184

Alfa AF: 0.160 Hom.: 1696

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	-0.84
CADD	Benign	0.41
DANN	Benign	0.53
BranchPoint Hunter		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000066
dbscSNV1_RF	Benign	0.0080
SpliceAI score (max)		0.10		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2516478; hg19: chr6-31498737; COSMIC: COSV66020876; COSMIC: COSV66020876;