rs497179

Variant names:

• chr4-168316513-G-A
• rs497179
• NM_017631.6:c.-107+2109C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017631.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX60	NM_017631.6	MANE Select	c.-107+2109C>T		intron	N/A	NP_060101.3
	DDX60	NM_001410861.1		c.-107+2109C>T		intron	N/A	NP_001397790.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DDX60	ENST00000393743.8	TSL:1 MANE Select	c.-107+2109C>T		intron	N/A	ENSP00000377344.3
	DDX60	ENST00000902213.1		c.-107+1661C>T		intron	N/A	ENSP00000572272.1
	DDX60	ENST00000680771.1		c.-107+2109C>T		intron	N/A	ENSP00000505292.1

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

African (AFR) AF: 0.551 AC: 22800 AN: 41414

American (AMR) AF: 0.335 AC: 5123 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1211 AN: 3466

East Asian (EAS) AF: 0.230 AC: 1185 AN: 5160

South Asian (SAS) AF: 0.391 AC: 1883 AN: 4820

European-Finnish (FIN) AF: 0.368 AC: 3867 AN: 10518

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19617 AN: 67952

Other (OTH) AF: 0.358 AC: 757 AN: 2112

Alfa AF: 0.319 Hom.: 26111

Bravo AF: 0.379

Asia WGS AF: 0.338 AC: 1176 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	9.0
DANN	Benign	0.47
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs497179; hg19: chr4-169237664;