rs2271957

chr17-43521572-T-C

Variant summary

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

The NM_004941.3(DHX8):c.3263+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,605,630 control chromosomes in the GnomAD database, including 55,398 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (6304 hom., cov: 29)
  • Exomes 𝑓: 0.26 (49094 hom.)
• Consequence: DHX8 NM_004941.3 splice_region, intron
• Scores: Splicing: ADA: 0.000009513
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

Genes affected

DHX8 (HGNC:2749): (DEAH-box helicase 8) This gene is a member of the DEAH box polypeptide family. The encoded protein contains the DEAH (Asp-Glu-Ala-His) motif which is characteristic of all DEAH box proteins, and is thought to function as an ATP-dependent RNA helicase that regulates the release of spliced mRNAs from spliceosomes prior to their export from the nucleus. This protein may be required for the replication of human immunodeficiency virus type 1 (HIV-1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DHX8	NM_004941.3	c.3263+7T>C		splice_region_variant, intron_variant		ENST00000262415.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DHX8	ENST00000262415.8	c.3263+7T>C		splice_region_variant, intron_variant		1	NM_004941.3	P1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43033 AN: 151492 Hom.: 6287 Cov.: 29

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.338

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.285

GnomAD3 exomes AF: 0.267 AC: 66361 AN: 248666 Hom.: 9054 AF XY: 0.267 AC XY: 35861 AN XY: 134316

Gnomad AFR exome AF: 0.354

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.300

Gnomad EAS exome AF: 0.306

Gnomad SAS exome AF: 0.257

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.258 AC: 374863 AN: 1454020 Hom.: 49094 Cov.: 32 AF XY: 0.258 AC XY: 186405 AN XY: 721964

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.235

Gnomad4 ASJ exome AF: 0.300

Gnomad4 EAS exome AF: 0.364

Gnomad4 SAS exome AF: 0.261

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.249

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.284 AC: 43096 AN: 151610 Hom.: 6304 Cov.: 29 AF XY: 0.285 AC XY: 21093 AN XY: 74054

Gnomad4 AFR AF: 0.348

Gnomad4 AMR AF: 0.230

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.321

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.281

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.281

Alfa AF: 0.263 Hom.: 7056

Bravo AF: 0.284

Asia WGS AF: 0.241 AC: 839 AN: 3478

EpiCase AF: 0.265

EpiControl AF: 0.256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.9
Dann	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000095
dbscSNV1_RF	Benign	0.0
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: rs2271957; hg19: chr17-41598940; COSMIC: COSV52253553; COSMIC: COSV52253553;