rs1079661

Positions:

• chr20-49234077-A-T

Variant summary

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

The NM_017895.8(DDX27):​c.1273+368A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 205,356 control chromosomes in the GnomAD database, including 22,770 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 0.45 (16495 hom., cov: 32)
  • Exomes 𝑓: 0.47 (6275 hom.)
• Consequence: DDX27 NM_017895.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

Genes affected

DDX27 (HGNC:15837): (DEAD-box helicase 27) 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 involved in the processing of 5.8S and 28S ribosomal RNAs. More specifically, the encoded protein localizes to the nucleolus, where it interacts with the PeBoW complex to ensure proper 3' end formation of 47S rRNA. [provided by RefSeq, Jan 2017]

DDX27 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDX27	NM_017895.8	c.1273+368A>T		intron_variant		ENST00000618172.5	NP_060365.8
DDX27	NM_001348187.2	c.1366+368A>T		intron_variant			NP_001335116.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDX27	ENST00000618172.5	c.1273+368A>T		intron_variant		1	NM_017895.8	ENSP00000482680.1
DDX27	ENST00000471144.1	n.240A>T		non_coding_transcript_exon_variant	1/7	1
DDX27	ENST00000484427.5	n.1743A>T		non_coding_transcript_exon_variant	11/19	1

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67737 AN: 151914 Hom.: 16502 Cov.: 32

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.462

Gnomad FIN AF: 0.577

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.494

GnomAD4 exome AF: 0.472 AC: 25171 AN: 53324 Hom.: 6275 Cov.: 0 AF XY: 0.481 AC XY: 13179 AN XY: 27386

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.377

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.405

Gnomad4 SAS exome AF: 0.436

Gnomad4 FIN exome AF: 0.542

Gnomad4 NFE exome AF: 0.515

Gnomad4 OTH exome AF: 0.489

GnomAD4 genome AF: 0.445 AC: 67730 AN: 152032 Hom.: 16495 Cov.: 32 AF XY: 0.447 AC XY: 33243 AN XY: 74324

Gnomad4 AFR AF: 0.236

Gnomad4 AMR AF: 0.433

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.453

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.577

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.489

Alfa AF: 0.492 Hom.: 2403

Bravo AF: 0.429

Asia WGS AF: 0.442 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.5
DANN	Benign	0.62

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: rs1079661; hg19: chr20-47850614;