rs16947824

Variant names:

• chr17-64505387-G-A
• rs16947824
• NM_004396.5:c.45-545C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-64505387-G-A
• chr17-64505387-G-T

Variant summary

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

The NM_004396.5(DDX5):​c.45-545C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 467,866 control chromosomes in the GnomAD database, including 667 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 0.050 (298 hom., cov: 33)
  • Exomes 𝑓: 0.039 (369 hom.)
• Consequence: DDX5 NM_004396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 4 publications found

Genes affected

DDX5 (HGNC:2746): (DEAD-box helicase 5) This gene encodes a member of the DEAD box family of RNA helicases that are involved in a variety of cellular processes as a result of its role as an adaptor molecule, promoting interactions with a large number of other factors. This protein is involved in pathways that include the alteration of RNA structures, plays a role as a coregulator of transcription, a regulator of splicing, and in the processing of small noncoding RNAs. Members of this family contain nine conserved motifs, including the conserved Asp-Glu-Ala-Asp (DEAD) motif, important to ATP binding and hydrolysis as well as RNA binding and unwinding activities. Dysregulation of this gene may play a role in cancer development. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2017]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004396.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX5	NM_004396.5	MANE Select	c.45-545C>T		intron	N/A	NP_004387.1
	DDX5	NM_001320595.2		c.45-545C>T		intron	N/A	NP_001307524.1
	DDX5	NM_001320596.3		c.45-545C>T		intron	N/A	NP_001307525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX5	ENST00000225792.10	TSL:1 MANE Select	c.45-545C>T		intron	N/A	ENSP00000225792.5
	DDX5	ENST00000578804.5	TSL:1	c.44+359C>T		intron	N/A	ENSP00000462885.1
	DDX5	ENST00000578190.5	TSL:3	c.-440C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000463541.1

Frequencies

GnomAD3 genomes AF: 0.0498 AC: 7570 AN: 152146 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.135

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.0350

Gnomad FIN AF: 0.0446

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0404

Gnomad OTH AF: 0.0445

GnomAD4 exome AF: 0.0394 AC: 12430 AN: 315602 Hom.: 369 Cov.: 0 AF XY: 0.0388 AC XY: 6387 AN XY: 164546

African (AFR) AF: 0.0376 AC: 358 AN: 9522

American (AMR) AF: 0.125 AC: 1518 AN: 12178

Ashkenazi Jewish (ASJ) AF: 0.0338 AC: 341 AN: 10084

East Asian (EAS) AF: 0.0316 AC: 693 AN: 21918

South Asian (SAS) AF: 0.0309 AC: 1002 AN: 32462

European-Finnish (FIN) AF: 0.0428 AC: 810 AN: 18922

Middle Eastern (MID) AF: 0.0270 AC: 38 AN: 1410

European-Non Finnish (NFE) AF: 0.0363 AC: 6910 AN: 190408

Other (OTH) AF: 0.0406 AC: 760 AN: 18698

GnomAD4 genome AF: 0.0497 AC: 7567 AN: 152264 Hom.: 298 Cov.: 33 AF XY: 0.0526 AC XY: 3919 AN XY: 74470

African (AFR) AF: 0.0400 AC: 1662 AN: 41542

American (AMR) AF: 0.134 AC: 2057 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0435 AC: 151 AN: 3468

East Asian (EAS) AF: 0.0326 AC: 169 AN: 5188

South Asian (SAS) AF: 0.0352 AC: 170 AN: 4826

European-Finnish (FIN) AF: 0.0446 AC: 473 AN: 10612

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0404 AC: 2750 AN: 68012

Other (OTH) AF: 0.0440 AC: 93 AN: 2114

Alfa AF: 0.0400 Hom.: 344

Bravo AF: 0.0523

Asia WGS AF: 0.0340 AC: 118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.9
DANN	Benign	0.84
PhyloP100		0.34
PromoterAI		-0.031	Neutral
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: rs16947824; hg19: chr17-62501505;