12-31096291-T-C

Position:

• chr12-31096291-T-C

Variant summary

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

The ENST00000542838.6(DDX11):​c.1483-50T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 1,127,988 control chromosomes in the GnomAD database, including 99,063 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 0.53 (21853 hom., cov: 25)
  • Exomes 𝑓: 0.28 (77210 hom.)
• Consequence: DDX11 ENST00000542838.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.789 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX11	NM_030653.4	c.1483-50T>C		intron_variant		ENST00000542838.6	NP_085911.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX11	ENST00000542838.6	c.1483-50T>C		intron_variant		1	NM_030653.4	ENSP00000443426	P1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 77874 AN: 147120 Hom.: 21797 Cov.: 25

Gnomad AFR AF: 0.670

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.809

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.440

Gnomad OTH AF: 0.505

GnomAD3 exomes AF: 0.336 AC: 58292 AN: 173274 Hom.: 21596 AF XY: 0.320 AC XY: 29811 AN XY: 93290

Gnomad AFR exome AF: 0.467

Gnomad AMR exome AF: 0.558

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.722

Gnomad SAS exome AF: 0.401

Gnomad FIN exome AF: 0.221

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.344

GnomAD4 exome AF: 0.277 AC: 271899 AN: 980746 Hom.: 77210 Cov.: 31 AF XY: 0.285 AC XY: 141874 AN XY: 496952

Gnomad4 AFR exome AF: 0.524

Gnomad4 AMR exome AF: 0.564

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.814

Gnomad4 SAS exome AF: 0.459

Gnomad4 FIN exome AF: 0.353

Gnomad4 NFE exome AF: 0.206

Gnomad4 OTH exome AF: 0.337

GnomAD4 genome AF: 0.530 AC: 77988 AN: 147242 Hom.: 21853 Cov.: 25 AF XY: 0.531 AC XY: 38068 AN XY: 71716

Gnomad4 AFR AF: 0.670

Gnomad4 AMR AF: 0.590

Gnomad4 ASJ AF: 0.382

Gnomad4 EAS AF: 0.810

Gnomad4 SAS AF: 0.551

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.440

Gnomad4 OTH AF: 0.505

Alfa AF: 0.444 Hom.: 2964

Bravo AF: 0.560

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.8
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs9788047; hg19: chr12-31249225;