6-31539285-G-C

Variant names:

• chr6-31539285-G-C
• rs2071595
• NM_004640.7:c.212-11C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004640.7(DDX39B):​c.212-11C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0794 in 1,607,168 control chromosomes in the GnomAD database, including 6,754 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.085 (802 hom., cov: 32)
  • Exomes 𝑓: 0.079 (5952 hom.)
• Consequence: DDX39B NM_004640.7 intron
• Scores: Splicing: ADA: 0.0009793
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.899
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004640.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	NM_004640.7	MANE Select	c.212-11C>G		intron	N/A	NP_004631.1	Q13838-1
	DDX39B	NM_080598.6		c.212-11C>G		intron	N/A	NP_542165.1	Q13838-1
	DDX39B	NR_037852.2		n.397+1037C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX39B	ENST00000396172.6	TSL:1 MANE Select	c.212-11C>G		intron	N/A	ENSP00000379475.1	Q13838-1
	DDX39B	ENST00000458640.5	TSL:1	c.212-11C>G		intron	N/A	ENSP00000416269.1	Q13838-1
	ATP6V1G2-DDX39B	ENST00000376185.5	TSL:2	n.*426-11C>G		intron	N/A	ENSP00000365356.1	F2Z307

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12874 AN: 151924 Hom.: 802 Cov.: 32

Gnomad AFR AF: 0.0519

Gnomad AMI AF: 0.131

Gnomad AMR AF: 0.0583

Gnomad ASJ AF: 0.0915

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0748

Gnomad OTH AF: 0.0721

GnomAD2 exomes AF: 0.0988 AC: 24112 AN: 244144 AF XY: 0.104

Gnomad AFR exome AF: 0.0471

Gnomad AMR exome AF: 0.0399

Gnomad ASJ exome AF: 0.0944

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.219

Gnomad NFE exome AF: 0.0789

Gnomad OTH exome AF: 0.0976

GnomAD4 exome AF: 0.0789 AC: 114781 AN: 1455124 Hom.: 5952 Cov.: 33 AF XY: 0.0823 AC XY: 59501 AN XY: 722622

African (AFR) AF: 0.0482 AC: 1608 AN: 33366

American (AMR) AF: 0.0426 AC: 1898 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.0946 AC: 2466 AN: 26056

East Asian (EAS) AF: 0.155 AC: 6117 AN: 39536

South Asian (SAS) AF: 0.164 AC: 14097 AN: 86154

European-Finnish (FIN) AF: 0.209 AC: 10938 AN: 52328

Middle Eastern (MID) AF: 0.134 AC: 770 AN: 5750

European-Non Finnish (NFE) AF: 0.0652 AC: 72198 AN: 1107282

Other (OTH) AF: 0.0781 AC: 4689 AN: 60058

GnomAD4 genome AF: 0.0847 AC: 12883 AN: 152044 Hom.: 802 Cov.: 32 AF XY: 0.0949 AC XY: 7055 AN XY: 74330

African (AFR) AF: 0.0520 AC: 2155 AN: 41478

American (AMR) AF: 0.0582 AC: 889 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0915 AC: 317 AN: 3464

East Asian (EAS) AF: 0.145 AC: 748 AN: 5174

South Asian (SAS) AF: 0.187 AC: 899 AN: 4816

European-Finnish (FIN) AF: 0.236 AC: 2494 AN: 10546

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0748 AC: 5083 AN: 67968

Other (OTH) AF: 0.0723 AC: 153 AN: 2116

Alfa AF: 0.0581 Hom.: 76

Bravo AF: 0.0655

Asia WGS AF: 0.122 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.36
DANN	Benign	0.71
PhyloP100		-0.90
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00098
dbscSNV1_RF	Benign	0.036
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: rs2071595; hg19: chr6-31507062; COSMIC: COSV107456310; COSMIC: COSV107456310;