chr6-31542328-A-G

Position:

• chr6-31542328-A-G

Variant summary

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

The NR_133674.1(DDX39B-AS1):​n.25A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.754 in 683,760 control chromosomes in the GnomAD database, including 195,635 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 0.76 (44694 hom., cov: 33)
  • Exomes 𝑓: 0.75 (150941 hom.)
• Consequence: DDX39B-AS1 NR_133674.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.464

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]

DDX39B-AS1 (HGNC:39771): (DDX39B antisense RNA 1)

ATP6V1G2-DDX39B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX39B-AS1	NR_133674.1	n.25A>G		non_coding_transcript_exon_variant	1/2
ATP6V1G2-DDX39B	NR_037853.1	n.473-180T>C		intron_variant, non_coding_transcript_variant
DDX39B-AS1	NR_133675.1	n.25A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000458640.5	c.-381T>C		5_prime_UTR_variant	1/11	1		ENSP00000416269	P1
DDX39B-AS1	ENST00000420520.1	n.25A>G		non_coding_transcript_exon_variant	1/2	3
DDX39B	ENST00000482195.5	n.74T>C		non_coding_transcript_exon_variant	1/6	2
DDX39B-AS1	ENST00000416684.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116027 AN: 152002 Hom.: 44647 Cov.: 33

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.821

Gnomad SAS AF: 0.743

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.736

Gnomad OTH AF: 0.788

GnomAD3 exomes AF: 0.773 AC: 105858 AN: 136984 Hom.: 41156 AF XY: 0.771 AC XY: 57368 AN XY: 74366

Gnomad AFR exome AF: 0.826

Gnomad AMR exome AF: 0.816

Gnomad ASJ exome AF: 0.852

Gnomad EAS exome AF: 0.849

Gnomad SAS exome AF: 0.758

Gnomad FIN exome AF: 0.599

Gnomad NFE exome AF: 0.744

Gnomad OTH exome AF: 0.771

GnomAD4 exome AF: 0.751 AC: 399255 AN: 531640 Hom.: 150941 Cov.: 0 AF XY: 0.752 AC XY: 216810 AN XY: 288436

Gnomad4 AFR exome AF: 0.831

Gnomad4 AMR exome AF: 0.822

Gnomad4 ASJ exome AF: 0.845

Gnomad4 EAS exome AF: 0.777

Gnomad4 SAS exome AF: 0.757

Gnomad4 FIN exome AF: 0.617

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.763 AC: 116132 AN: 152120 Hom.: 44694 Cov.: 33 AF XY: 0.758 AC XY: 56369 AN XY: 74362

Gnomad4 AFR AF: 0.824

Gnomad4 AMR AF: 0.810

Gnomad4 ASJ AF: 0.849

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.742

Gnomad4 FIN AF: 0.588

Gnomad4 NFE AF: 0.736

Gnomad4 OTH AF: 0.789

Alfa AF: 0.757 Hom.: 66502

Bravo AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	6.7
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs2239528; hg19: chr6-31510105;