rs9750

Positions:

• chr12-31104530-G-A

Variant summary

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

The NM_030653.4(DDX11):​c.*694G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 171,198 control chromosomes in the GnomAD database, including 25,988 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 0.54 (23458 hom., cov: 34)
  • Exomes 𝑓: 0.48 (2530 hom.)
• Consequence: DDX11 NM_030653.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.199

Genes affected

DDX11 (HGNC:2736): (DEAD/H-box helicase 11) 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 an enzyme that possesses both ATPase and DNA helicase activities. This gene is a homolog of the yeast CHL1 gene, and may function to maintain chromosome transmission fidelity and genome stability. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

DDX11 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX11	NM_030653.4	c.*694G>A		3_prime_UTR_variant	27/27	ENST00000542838.6	NP_085911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX11	ENST00000542838.6	c.*694G>A		3_prime_UTR_variant	27/27	1	NM_030653.4	ENSP00000443426.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82252 AN: 151970 Hom.: 23403 Cov.: 34

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.598

Gnomad ASJ AF: 0.388

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.571

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.526

GnomAD4 exome AF: 0.483 AC: 9222 AN: 19110 Hom.: 2530 Cov.: 0 AF XY: 0.489 AC XY: 4833 AN XY: 9884

Gnomad4 AFR exome AF: 0.606

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.815

Gnomad4 SAS exome AF: 0.525

Gnomad4 FIN exome AF: 0.323

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.444

GnomAD4 genome AF: 0.542 AC: 82361 AN: 152088 Hom.: 23458 Cov.: 34 AF XY: 0.544 AC XY: 40434 AN XY: 74358

Gnomad4 AFR AF: 0.679

Gnomad4 AMR AF: 0.598

Gnomad4 ASJ AF: 0.388

Gnomad4 EAS AF: 0.818

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.525

Alfa AF: 0.495 Hom.: 2428

Bravo AF: 0.564

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	6.1
DANN	Benign	0.69
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9750; hg19: chr12-31257464;