Variant rs2271957 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Variant links:

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]

DHX8 links:

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ACMG classification

Classification made for transcript

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	Protein	UniProt
DHX8	NM_004941.3 linkuse as main transcript	c.3263+7T>C		splice_region_variant, intron_variant		ENST00000262415.8	NP_004932.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHX8	ENST00000262415.8 linkuse as main transcript	c.3263+7T>C		splice_region_variant, intron_variant		1	NM_004941.3	ENSP00000262415	P1

Frequencies

GnomAD3 genomes

AF:

0.284

AC:

43033

AN:

151492

Hom.:

6287

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.258

AC XY:

186405

AN XY:

721964

show subpopulations

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.:

AF XY:

0.285

AC XY:

21093

AN XY:

74054

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over