rs3130059

Variant names:

• chr6-31541507-G-C
• rs3130059
• NM_004640.7:c.-133+443C>G

Your query was ambiguous. Multiple possible variants found:

• chr6-31541507-G-C
• chr6-31541507-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.-133+443C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 390,888 control chromosomes in the GnomAD database, including 25,607 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 0.38 (11611 hom., cov: 31)
  • Exomes 𝑓: 0.33 (13996 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.110
• 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]

ENSG00000299760 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.-133+443C>G		intron_variant	Intron 1 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.-3+443C>G		intron_variant	Intron 1 of 10		NP_542165.1
DDX39B	NR_037852.2	n.54+443C>G		intron_variant	Intron 1 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.671+443C>G		intron_variant	Intron 3 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.-133+443C>G		intron_variant	Intron 1 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*82+443C>G		intron_variant	Intron 3 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58150 AN: 151694 Hom.: 11599 Cov.: 31

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.281

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.356

GnomAD4 exome AF: 0.334 AC: 79829 AN: 239076 Hom.: 13996 Cov.: 0 AF XY: 0.328 AC XY: 43696 AN XY: 133306

African (AFR) AF: 0.504 AC: 2821 AN: 5600

American (AMR) AF: 0.336 AC: 4342 AN: 12908

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 1428 AN: 5492

East Asian (EAS) AF: 0.499 AC: 4272 AN: 8564

South Asian (SAS) AF: 0.286 AC: 13206 AN: 46116

European-Finnish (FIN) AF: 0.309 AC: 7430 AN: 24036

Middle Eastern (MID) AF: 0.408 AC: 832 AN: 2038

European-Non Finnish (NFE) AF: 0.339 AC: 41854 AN: 123532

Other (OTH) AF: 0.338 AC: 3644 AN: 10790

GnomAD4 genome AF: 0.383 AC: 58201 AN: 151812 Hom.: 11611 Cov.: 31 AF XY: 0.379 AC XY: 28137 AN XY: 74198

African (AFR) AF: 0.502 AC: 20786 AN: 41374

American (AMR) AF: 0.348 AC: 5315 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3470

East Asian (EAS) AF: 0.474 AC: 2442 AN: 5156

South Asian (SAS) AF: 0.282 AC: 1356 AN: 4812

European-Finnish (FIN) AF: 0.303 AC: 3188 AN: 10530

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23062 AN: 67900

Other (OTH) AF: 0.354 AC: 747 AN: 2110

Alfa AF: 0.350 Hom.: 5312

Bravo AF: 0.392

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.2
DANN	Benign	0.52
PhyloP100		-0.11
PromoterAI		-0.035	Neutral
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: rs3130059; hg19: chr6-31509284; COSMIC: COSV107335999; COSMIC: COSV107335999;