17-42109527-C-T

Variant names:

• chr17-42109527-C-T
• rs12600570
• NM_024119.3:c.562-141G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
DHX58	NM_024119.3	c.562-141G>A		intron_variant	Intron 5 of 13	ENST00000251642.8	NP_077024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX58	ENST00000251642.8	c.562-141G>A		intron_variant	Intron 5 of 13	1	NM_024119.3	ENSP00000251642.3
DHX58	ENST00000413196.6	c.562-141G>A		intron_variant	Intron 4 of 6	5		ENSP00000416389.1
DHX58	ENST00000586522.5	n.744-141G>A		intron_variant	Intron 5 of 11	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

African (AFR) AF: 0.379 AC: 5158 AN: 13614

American (AMR) AF: 0.103 AC: 2032 AN: 19682

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 1493 AN: 14184

East Asian (EAS) AF: 0.160 AC: 4841 AN: 30238

South Asian (SAS) AF: 0.141 AC: 5886 AN: 41740

European-Finnish (FIN) AF: 0.118 AC: 3631 AN: 30780

Middle Eastern (MID) AF: 0.136 AC: 481 AN: 3524

European-Non Finnish (NFE) AF: 0.104 AC: 32701 AN: 314628

Other (OTH) AF: 0.141 AC: 3886 AN: 27482

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

African (AFR) AF: 0.384 AC: 15903 AN: 41444

American (AMR) AF: 0.129 AC: 1969 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3470

East Asian (EAS) AF: 0.157 AC: 814 AN: 5178

South Asian (SAS) AF: 0.162 AC: 781 AN: 4824

European-Finnish (FIN) AF: 0.126 AC: 1339 AN: 10590

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.111 AC: 7537 AN: 67998

Other (OTH) AF: 0.169 AC: 357 AN: 2112

Alfa AF: 0.136 Hom.: 1925

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
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12600570; hg19: chr17-40261545;