rs497179

chr4-168316513-G-A

Variant summary

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

The NM_017631.6(DDX60):c.-107+2109C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 151,922 control chromosomes in the GnomAD database, including 11,605 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 0.37 (11605 hom., cov: 32)
• Consequence: DDX60 NM_017631.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

Genes affected

DDX60 (HGNC:25942): (DExD/H-box helicase 60) DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases which are implicated in a number of cellular procsses involving RNA binding and alteration of RNA secondary structure. This gene encodes a DEXD/H box RNA helicase that functions as an antiviral factor and promotes RIG-I-like receptor-mediated signaling. [provided by RefSeq, Apr 2017]

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 (AFR) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDX60	NM_017631.6	c.-107+2109C>T		intron_variant		ENST00000393743.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDX60	ENST00000393743.8	c.-107+2109C>T		intron_variant		1	NM_017631.6	P2

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56744 AN: 151804 Hom.: 11582 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.359

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.374 AC: 56817 AN: 151922 Hom.: 11605 Cov.: 32 AF XY: 0.374 AC XY: 27775 AN XY: 74268

Gnomad4 AFR AF: 0.551

Gnomad4 AMR AF: 0.335

Gnomad4 ASJ AF: 0.349

Gnomad4 EAS AF: 0.230

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.358

Alfa AF: 0.304 Hom.: 14680

Bravo AF: 0.379

Asia WGS AF: 0.338 AC: 1176 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	9.0
Dann	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs497179; hg19: chr4-169237664;