rs12600570

Positions:

• chr17-42109527-C-T

Variant summary

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

The NM_024119.3(DHX58):​c.562-141G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 647,980 control chromosomes in the GnomAD database, including 8,461 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 0.19 (3944 hom., cov: 33)
  • Exomes 𝑓: 0.12 (4517 hom.)
• Consequence: DHX58 NM_024119.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09

Genes affected

DHX58 (HGNC:29517): (DExH-box helicase 58) Enables double-stranded RNA binding activity; single-stranded RNA binding activity; and zinc ion binding activity. Involved in negative regulation of defense response and negative regulation of type I interferon production. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DHX58 (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 (AFR) allele frequency at 95% confidence interval = 0.379 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHX58	NM_024119.3	c.562-141G>A		intron_variant		ENST00000251642.8	NP_077024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX58	ENST00000251642.8	c.562-141G>A		intron_variant		1	NM_024119.3	ENSP00000251642.3
DHX58	ENST00000413196.6	c.562-141G>A		intron_variant		5		ENSP00000416389.1
DHX58	ENST00000586522.5	n.744-141G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.192 AC: 29187 AN: 151988 Hom.: 3940 Cov.: 33

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.126

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.121 AC: 60109 AN: 495872 Hom.: 4517 AF XY: 0.120 AC XY: 30768 AN XY: 256952

Gnomad4 AFR exome AF: 0.379

Gnomad4 AMR exome AF: 0.103

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.141

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.104

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.192 AC: 29213 AN: 152108 Hom.: 3944 Cov.: 33 AF XY: 0.190 AC XY: 14148 AN XY: 74372

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.157

Gnomad4 SAS AF: 0.162

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.169

Alfa AF: 0.123 Hom.: 1057

Bravo AF: 0.199

Asia WGS AF: 0.205 AC: 712 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	0.61
DANN	Benign	0.59

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: rs12600570; hg19: chr17-40261545;