5-55801706-G-A

Position:

• chr5-55801706-G-A

Variant summary

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

The NM_024415.3(DDX4):​c.1615+3135G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,916 control chromosomes in the GnomAD database, including 9,674 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 0.34 (9674 hom., cov: 32)
• Consequence: DDX4 NM_024415.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

DDX4 (HGNC:18700): (DEAD-box helicase 4) 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 family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. This gene encodes a DEAD box protein, which is a homolog of VASA proteins in Drosophila and several other species. The gene is specifically expressed in the germ cell lineage in both sexes and functions in germ cell development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX4	NM_024415.3	c.1615+3135G>A		intron_variant		ENST00000505374.6	NP_077726.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX4	ENST00000505374.6	c.1615+3135G>A		intron_variant		1	NM_024415.3	ENSP00000424838.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51630 AN: 151798 Hom.: 9657 Cov.: 32

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.475

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.264

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.340 AC: 51702 AN: 151916 Hom.: 9674 Cov.: 32 AF XY: 0.339 AC XY: 25145 AN XY: 74252

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.253

Gnomad4 EAS AF: 0.475

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.264

Gnomad4 OTH AF: 0.327

Alfa AF: 0.279 Hom.: 2924

Bravo AF: 0.371

Asia WGS AF: 0.384 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.6
DANN	Benign	0.52

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: rs2619046; hg19: chr5-55097534;