chr6-31536198-G-C

Variant names:

• chr6-31536198-G-C
• rs2075580
• NM_004640.7:c.616+302C>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.616+302C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,098 control chromosomes in the GnomAD database, including 44,618 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 (44618 hom., cov: 32)
• Consequence: DDX39B NM_004640.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• Publications: 17 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]

SNORD117 (HGNC:32742): (small nucleolar RNA, C/D box 117)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX39B	NM_004640.7	c.616+302C>G		intron_variant	Intron 5 of 10	ENST00000396172.6	NP_004631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX39B	ENST00000396172.6	c.616+302C>G		intron_variant	Intron 5 of 10	1	NM_004640.7	ENSP00000379475.1
ATP6V1G2-DDX39B	ENST00000376185.5	n.*830+302C>G		intron_variant	Intron 7 of 12	2		ENSP00000365356.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 115919 AN: 151980 Hom.: 44571 Cov.: 32

Gnomad AFR AF: 0.824

Gnomad AMI AF: 0.698

Gnomad AMR AF: 0.810

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.739

Gnomad FIN AF: 0.587

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.738

Gnomad OTH AF: 0.788

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.763 AC: 116025 AN: 152098 Hom.: 44618 Cov.: 32 AF XY: 0.757 AC XY: 56267 AN XY: 74338

African (AFR) AF: 0.824 AC: 34171 AN: 41454

American (AMR) AF: 0.810 AC: 12383 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2945 AN: 3470

East Asian (EAS) AF: 0.782 AC: 4056 AN: 5188

South Asian (SAS) AF: 0.737 AC: 3558 AN: 4826

European-Finnish (FIN) AF: 0.587 AC: 6210 AN: 10578

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.738 AC: 50165 AN: 67986

Other (OTH) AF: 0.788 AC: 1662 AN: 2108

Alfa AF: 0.667 Hom.: 2109

Bravo AF: 0.785

Asia WGS AF: 0.744 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.5
DANN	Benign	0.63
PhyloP100		-0.0030
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: rs2075580; hg19: chr6-31503975;