6-31533435-A-T

Variant names:

• chr6-31533435-A-T
• rs11796
• NM_004640.7:c.736-524T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B.

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_004640.7(DDX39B):​c.736-524T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 159,848 control chromosomes in the GnomAD database, including 11,986 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 (11536 hom., cov: 31)
  • Exomes 𝑓: 0.32 (450 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.581
• Publications: 30 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.736-524T>A		intron_variant	Intron 6 of 10	ENST00000396172.6	NP_004631.1
DDX39B	NM_080598.6	c.736-524T>A		intron_variant	Intron 6 of 10		NP_542165.1
DDX39B	NR_037852.2	n.701-524T>A		intron_variant	Intron 4 of 8
ATP6V1G2-DDX39B	NR_037853.1	n.1539-524T>A		intron_variant	Intron 8 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.736-524T>A		intron_variant	Intron 6 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*950-524T>A		intron_variant	Intron 8 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 57954 AN: 151740 Hom.: 11524 Cov.: 31

Gnomad AFR AF: 0.505

Gnomad AMI AF: 0.367

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.303

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.354

GnomAD4 exome AF: 0.321 AC: 2564 AN: 7990 Hom.: 450 Cov.: 0 AF XY: 0.314 AC XY: 1317 AN XY: 4196

African (AFR) AF: 0.333 AC: 10 AN: 30

American (AMR) AF: 0.314 AC: 551 AN: 1754

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 20 AN: 72

East Asian (EAS) AF: 0.436 AC: 41 AN: 94

South Asian (SAS) AF: 0.275 AC: 359 AN: 1306

European-Finnish (FIN) AF: 0.349 AC: 65 AN: 186

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.336 AC: 1414 AN: 4214

Other (OTH) AF: 0.314 AC: 103 AN: 328

GnomAD4 genome AF: 0.382 AC: 58008 AN: 151858 Hom.: 11536 Cov.: 31 AF XY: 0.377 AC XY: 28000 AN XY: 74204

African (AFR) AF: 0.505 AC: 20860 AN: 41346

American (AMR) AF: 0.347 AC: 5301 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 872 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2249 AN: 5176

South Asian (SAS) AF: 0.265 AC: 1272 AN: 4806

European-Finnish (FIN) AF: 0.303 AC: 3192 AN: 10538

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23087 AN: 67946

Other (OTH) AF: 0.352 AC: 743 AN: 2112

Alfa AF: 0.350 Hom.: 5333

Bravo AF: 0.391

Asia WGS AF: 0.321 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.85
PhyloP100		0.58
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: rs11796; hg19: chr6-31501212;