rs7953706

Positions:

• chr12-31073901-T-A
• chr12-31073901-T-C
• chr12-31073901-T-G

Variant summary

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

The NM_030653.4(DDX11):​c.-195T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,182 control chromosomes in the GnomAD database, including 22,686 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 (22685 hom., cov: 33)
  • Exomes 𝑓: 0.35 (1 hom.)
• Consequence: DDX11 NM_030653.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX11	NM_030653.4	c.-195T>A		5_prime_UTR_variant	1/27	ENST00000542838.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX11	ENST00000542838.6	c.-195T>A		5_prime_UTR_variant	1/27	1	NM_030653.4	P1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80891 AN: 152044 Hom.: 22631 Cov.: 33

Gnomad AFR AF: 0.658

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.816

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.444

Gnomad OTH AF: 0.515

GnomAD4 exome AF: 0.350 AC: 7 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.375 AC XY: 6 AN XY: 16

Gnomad4 NFE exome AF: 0.333

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.532 AC: 81000 AN: 152162 Hom.: 22685 Cov.: 33 AF XY: 0.535 AC XY: 39784 AN XY: 74388

Gnomad4 AFR AF: 0.659

Gnomad4 AMR AF: 0.593

Gnomad4 ASJ AF: 0.386

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.569

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.444

Gnomad4 OTH AF: 0.515

Alfa AF: 0.487 Hom.: 2342

Bravo AF: 0.553

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.3
DANN	Benign	0.65

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: rs7953706; hg19: chr12-31226835;