rs3853601

Variant names:

• chr6-31531826-C-G
• rs3853601
• NM_004640.7:c.868-421G>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.868-421G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 172,498 control chromosomes in the GnomAD database, including 1,457 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 0.13 (1328 hom., cov: 31)
  • Exomes 𝑓: 0.090 (129 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 24 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.868-421G>C		intron_variant	Intron 7 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.868-421G>C		intron_variant	Intron 7 of 10		NP_542165.1
DDX39B	NR_037852.2	n.833-421G>C		intron_variant	Intron 5 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1671-421G>C		intron_variant	Intron 9 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.868-421G>C		intron_variant	Intron 7 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*1082-421G>C		intron_variant	Intron 9 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19230 AN: 151910 Hom.: 1328 Cov.: 31

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.113

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0193

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.0901 AC: 1845 AN: 20470 Hom.: 129 AF XY: 0.0889 AC XY: 968 AN XY: 10890

African (AFR) AF: 0.164 AC: 47 AN: 286

American (AMR) AF: 0.0764 AC: 217 AN: 2842

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 52 AN: 348

East Asian (EAS) AF: 0.0412 AC: 39 AN: 946

South Asian (SAS) AF: 0.0289 AC: 81 AN: 2806

European-Finnish (FIN) AF: 0.0893 AC: 40 AN: 448

Middle Eastern (MID) AF: 0.214 AC: 6 AN: 28

European-Non Finnish (NFE) AF: 0.108 AC: 1280 AN: 11860

Other (OTH) AF: 0.0916 AC: 83 AN: 906

GnomAD4 genome AF: 0.127 AC: 19241 AN: 152028 Hom.: 1328 Cov.: 31 AF XY: 0.124 AC XY: 9210 AN XY: 74316

African (AFR) AF: 0.171 AC: 7092 AN: 41444

American (AMR) AF: 0.0983 AC: 1501 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3470

East Asian (EAS) AF: 0.0194 AC: 100 AN: 5160

South Asian (SAS) AF: 0.0376 AC: 181 AN: 4812

European-Finnish (FIN) AF: 0.121 AC: 1283 AN: 10580

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8167 AN: 67974

Other (OTH) AF: 0.122 AC: 257 AN: 2108

Alfa AF: 0.124 Hom.: 672

Bravo AF: 0.128

Asia WGS AF: 0.0500 AC: 175 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	0.014
DANN	Benign	0.66
PhyloP100		-2.3
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: rs3853601; hg19: chr6-31499603;