rs2071596

Variant names:

• chr6-31538914-G-A
• rs2071596
• NM_004640.7:c.340-59C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31538914-G-A
• chr6-31538914-G-C
• chr6-31538914-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.340-59C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.179 in 1,563,490 control chromosomes in the GnomAD database, including 27,338 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 0.22 (3928 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23410 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.24
• Publications: 39 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 (MetaRNN=0.0035931468).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.340-59C>T		intron_variant	Intron 3 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.340-59C>T		intron_variant	Intron 3 of 10		NP_542165.1
DDX39B	NR_037852.2	n.397+1408C>T		intron_variant	Intron 2 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1143-59C>T		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.340-59C>T		intron_variant	Intron 3 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*554-59C>T		intron_variant	Intron 5 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33047 AN: 151862 Hom.: 3929 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.180

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.203

GnomAD2 exomes AF: 0.203 AC: 50782 AN: 250300 AF XY: 0.192

Gnomad AFR exome AF: 0.308

Gnomad AMR exome AF: 0.270

Gnomad ASJ exome AF: 0.174

Gnomad EAS exome AF: 0.364

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.175 AC: 246668 AN: 1411508 Hom.: 23410 Cov.: 26 AF XY: 0.171 AC XY: 120885 AN XY: 705202

African (AFR) AF: 0.312 AC: 10072 AN: 32286

American (AMR) AF: 0.264 AC: 11760 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 4538 AN: 25782

East Asian (EAS) AF: 0.367 AC: 14485 AN: 39420

South Asian (SAS) AF: 0.122 AC: 10384 AN: 85070

European-Finnish (FIN) AF: 0.188 AC: 10019 AN: 53366

Middle Eastern (MID) AF: 0.183 AC: 1039 AN: 5690

European-Non Finnish (NFE) AF: 0.163 AC: 173492 AN: 1066702

Other (OTH) AF: 0.186 AC: 10879 AN: 58646

GnomAD4 genome AF: 0.218 AC: 33077 AN: 151982 Hom.: 3928 Cov.: 32 AF XY: 0.218 AC XY: 16187 AN XY: 74270

African (AFR) AF: 0.303 AC: 12529 AN: 41378

American (AMR) AF: 0.248 AC: 3780 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.167 AC: 581 AN: 3472

East Asian (EAS) AF: 0.361 AC: 1868 AN: 5176

South Asian (SAS) AF: 0.128 AC: 619 AN: 4824

European-Finnish (FIN) AF: 0.180 AC: 1907 AN: 10566

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11170 AN: 67986

Other (OTH) AF: 0.203 AC: 428 AN: 2108

Alfa AF: 0.185 Hom.: 9181

Bravo AF: 0.229

TwinsUK AF: 0.174 AC: 647

ALSPAC AF: 0.179 AC: 689

ExAC AF: 0.201 AC: 24352

Asia WGS AF: 0.228 AC: 795 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	8.5
DANN	Benign	0.79
DEOGEN2	Benign	0.0060	.;T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.14	N
MetaRNN	Benign	0.0036	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		1.2
PROVEAN	Benign	-0.42	N;N
REVEL	Benign	0.012
Sift	Benign	0.18	T;D
Sift4G	Uncertain	0.030	D;.
ClinPred		0.00058	T
GERP RS		-0.32
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
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: rs2071596; hg19: chr6-31506691; COSMIC: COSV63331076; COSMIC: COSV63331076;