dbSNP rs2271957: DHX8:c.3263+7T>C (chr17-43521572-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

14 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004941.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DHX8	NM_004941.3	MANE Select	c.3263+7T>C	splice_region intron	N/A	NP_004932.1	Q14562
DHX8	NM_001322221.2		c.3257+7T>C	splice_region intron	N/A	NP_001309150.1
DHX8	NM_001302623.3		c.3263+7T>C	splice_region intron	N/A	NP_001289552.1	F5H658

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DHX8	ENST00000262415.8	TSL:1 MANE Select	c.3263+7T>C	splice_region intron	N/A	ENSP00000262415.2	Q14562
DHX8	ENST00000958205.1		c.3359+7T>C	splice_region intron	N/A	ENSP00000628264.1
DHX8	ENST00000958204.1		c.3284+7T>C	splice_region intron	N/A	ENSP00000628263.1

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

GnomAD2 exomes

AF:

0.267

AC:

66361

AN:

248666

AF XY:

0.267

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 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

African (AFR)

AF:

0.358

AC:

11949

AN:

33368

American (AMR)

AF:

0.235

AC:

10453

AN:

44524

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

7779

AN:

25898

East Asian (EAS)

AF:

0.364

AC:

14365

AN:

39518

South Asian (SAS)

AF:

0.261

AC:

22409

AN:

85770

European-Finnish (FIN)

AF:

0.279

AC:

14844

AN:

53246

Middle Eastern (MID)

AF:

0.308

AC:

1766

AN:

5736

European-Non Finnish (NFE)

AF:

0.249

AC:

275807

AN:

1105922

Other (OTH)

AF:

0.258

AC:

15491

AN:

60038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

13755

27510

41266

55021

68776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9442

18884

28326

37768

47210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.284

AC:

43096

AN:

151610

Hom.:

6304

Cov.:

AF XY:

0.285

AC XY:

21093

AN XY:

74054

show subpopulations

African (AFR)

AF:

0.348

AC:

14385

AN:

41300

American (AMR)

AF:

0.230

AC:

3508

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.309

AC:

1070

AN:

3462

East Asian (EAS)

AF:

0.321

AC:

1629

AN:

5068

South Asian (SAS)

AF:

0.265

AC:

1279

AN:

4818

European-Finnish (FIN)

AF:

0.281

AC:

2950

AN:

10488

Middle Eastern (MID)

AF:

0.339

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.256

AC:

17370

AN:

67914

Other (OTH)

AF:

0.281

AC:

592

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1561

3122

4684

6245

7806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

456

912

1368

1824

2280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.263

Hom.:

8668

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

(source)

DANN

Benign

0.45

PhyloP100

-0.049

PromoterAI

0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over