17-5450757-C-T

Variant names:

• chr17-5450757-C-T
• rs3744714
• NM_020162.4:c.1524+50G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020162.4(DHX33):​c.1524+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 1,610,142 control chromosomes in the GnomAD database, including 27,268 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 0.15 (2838 hom., cov: 32)
  • Exomes 𝑓: 0.15 (24430 hom.)
• Consequence: DHX33 NM_020162.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.949
• Publications: 24 publications found

Genes affected

DHX33 (HGNC:16718): (DEAH-box helicase 33) This gene encodes a member of the DEAD box protein family. The DEAD box proteins are 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 DEAD box protein family are believed to be involved in embryogenesis, spermatogenesis, and cellular growth and division. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.624 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHX33	NM_020162.4	c.1524+50G>A		intron_variant	Intron 9 of 11	ENST00000225296.8	NP_064547.2
DHX33	NM_001199699.2	c.1005+50G>A		intron_variant	Intron 8 of 10		NP_001186628.1
DHX33	XM_047436418.1	c.1397-351G>A		intron_variant	Intron 8 of 8		XP_047292374.1
DHX33	XM_017024877.2	c.240+50G>A		intron_variant	Intron 5 of 7		XP_016880366.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHX33	ENST00000225296.8	c.1524+50G>A		intron_variant	Intron 9 of 11	1	NM_020162.4	ENSP00000225296.3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22179 AN: 151924 Hom.: 2844 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.237

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.146

GnomAD2 exomes AF: 0.218 AC: 54491 AN: 249538 AF XY: 0.214

Gnomad AFR exome AF: 0.0475

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.141

Gnomad EAS exome AF: 0.642

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.185

GnomAD4 exome AF: 0.147 AC: 214439 AN: 1458100 Hom.: 24430 Cov.: 31 AF XY: 0.150 AC XY: 109108 AN XY: 725344

African (AFR) AF: 0.0425 AC: 1418 AN: 33374

American (AMR) AF: 0.337 AC: 14987 AN: 44408

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 3693 AN: 25954

East Asian (EAS) AF: 0.630 AC: 24965 AN: 39648

South Asian (SAS) AF: 0.294 AC: 25230 AN: 85744

European-Finnish (FIN) AF: 0.251 AC: 13379 AN: 53324

Middle Eastern (MID) AF: 0.103 AC: 590 AN: 5726

European-Non Finnish (NFE) AF: 0.108 AC: 120263 AN: 1109700

Other (OTH) AF: 0.165 AC: 9914 AN: 60222

GnomAD4 genome AF: 0.146 AC: 22186 AN: 152042 Hom.: 2838 Cov.: 32 AF XY: 0.159 AC XY: 11835 AN XY: 74326

African (AFR) AF: 0.0510 AC: 2114 AN: 41474

American (AMR) AF: 0.238 AC: 3634 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 471 AN: 3470

East Asian (EAS) AF: 0.642 AC: 3309 AN: 5152

South Asian (SAS) AF: 0.313 AC: 1507 AN: 4812

European-Finnish (FIN) AF: 0.274 AC: 2897 AN: 10566

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7844 AN: 67992

Other (OTH) AF: 0.147 AC: 310 AN: 2114

Alfa AF: 0.123 Hom.: 5078

Bravo AF: 0.139

Asia WGS AF: 0.440 AC: 1526 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.67
PhyloP100		-0.95
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3744714; hg19: chr17-5354077;