rs3740596

Variant names:

• chr10-68914422-A-G
• rs3740596
• NM_024045.2:c.1089+218A>G

Variant summary

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

The NM_024045.2(DDX50):​c.1089+218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 152,258 control chromosomes in the GnomAD database, including 306 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 0.057 (306 hom., cov: 33)
• Consequence: DDX50 NM_024045.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0810
• Publications: 1 publications found

Genes affected

DDX50 (HGNC:17906): (DExD-box helicase 50) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. They are implicated in a number of cellular processes involving alteration of RNA secondary structure such as translation initiation, nuclear and mitochondrial splicing, and ribosome and spliceosome assembly. Based on their distribution patterns, some members of this DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box enzyme that may be involved in ribosomal RNA synthesis or processing. This gene and DDX21, also called RH-II/GuA, have similar genomic structures and are in tandem orientation on chromosome 10, suggesting that the two genes arose by gene duplication in evolution. This gene has pseudogenes on chromosomes 2, 3 and 4. Alternative splicing of this gene generates multiple transcript variants, but the full length nature of all the other variants but one has not been defined. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DDX50	NM_024045.2	c.1089+218A>G		intron_variant	Intron 7 of 14	ENST00000373585.8	NP_076950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DDX50	ENST00000373585.8	c.1089+218A>G		intron_variant	Intron 7 of 14	1	NM_024045.2	ENSP00000362687.3
DDX50	ENST00000460470.1	n.296+218A>G		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.0574 AC: 8740 AN: 152140 Hom.: 306 Cov.: 33

Gnomad AFR AF: 0.0298

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.0505

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0654

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

GnomAD4 genome AF: 0.0574 AC: 8744 AN: 152258 Hom.: 306 Cov.: 33 AF XY: 0.0574 AC XY: 4270 AN XY: 74434

African (AFR) AF: 0.0297 AC: 1235 AN: 41558

American (AMR) AF: 0.0505 AC: 772 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 380 AN: 3472

East Asian (EAS) AF: 0.0206 AC: 107 AN: 5186

South Asian (SAS) AF: 0.0694 AC: 335 AN: 4826

European-Finnish (FIN) AF: 0.0807 AC: 856 AN: 10602

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0701 AC: 4766 AN: 68000

Other (OTH) AF: 0.0647 AC: 137 AN: 2116

Alfa AF: 0.0560 Hom.: 29

Bravo AF: 0.0545

Asia WGS AF: 0.0280 AC: 96 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.65
PhyloP100		-0.081
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: rs3740596; hg19: chr10-70674178;