Genetic Variant DHX15:p.Thr92Thr (chr4-24576474-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001358.3(DHX15):c.276G>A(p.Thr92Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 1,614,048 control chromosomes in the GnomAD database, including 1,229 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 0.054 ( 334 hom., cov: 32)

Exomes 𝑓: 0.028 ( 895 hom. )

Consequence

DHX15
NM_001358.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.415

Publications

17 publications found

Variant links:

Genes affected

DHX15 (HGNC:2738): (DEAH-box helicase 15) The protein encoded by this gene is a putative ATP-dependent RNA helicase implicated in pre-mRNA splicing. [provided by RefSeq, Jul 2008]

DHX15 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP7

Synonymous conserved (PhyloP=0.415 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
DHX15	NM_001358.3 link	c.276G>A	p.Thr92Thr	synonymous_variant	Exon 2 of 14	ENST00000336812.5	NP_001349.2
DHX15	XM_047449698.1 link	c.276G>A	p.Thr92Thr	synonymous_variant	Exon 2 of 11		XP_047305654.1
DHX15	XM_047449699.1 link	c.276G>A	p.Thr92Thr	synonymous_variant	Exon 2 of 11		XP_047305655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
DHX15	ENST00000336812.5 link	c.276G>A	p.Thr92Thr	synonymous_variant	Exon 2 of 14	1	NM_001358.3	ENSP00000336741.4
DHX15	ENST00000511553.5 link	n.527G>A		non_coding_transcript_exon_variant	Exon 3 of 3	4
DHX15	ENST00000513092.1 link	n.*76G>A		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0536

AC:

8146

AN:

152066

Hom.:

332

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.130

Gnomad AMR

AF:

0.0388

Gnomad ASJ

AF:

0.00836

Gnomad EAS

AF:

0.0431

Gnomad SAS

AF:

0.0427

Gnomad FIN

AF:

0.0671

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0399

AC:

10028

AN:

251474

AF XY:

0.0379

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0582

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.0491

Gnomad FIN exome

AF:

0.0601

Gnomad NFE exome

AF:

0.0222

Gnomad OTH exome

AF:

0.0301

GnomAD4 exome

AF:

0.0282

AC:

41163

AN:

1461864

Hom.:

895

Cov.:

AF XY:

0.0284

AC XY:

20671

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.113

AC:

3782

AN:

33480

American (AMR)

AF:

0.0557

AC:

2492

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

263

AN:

26136

East Asian (EAS)

AF:

0.0483

AC:

1916

AN:

39698

South Asian (SAS)

AF:

0.0405

AC:

3493

AN:

86258

European-Finnish (FIN)

AF:

0.0595

AC:

3178

AN:

53420

Middle Eastern (MID)

AF:

0.0257

AC:

148

AN:

5766

European-Non Finnish (NFE)

AF:

0.0216

AC:

24003

AN:

1111988

Other (OTH)

AF:

0.0313

AC:

1888

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

2824

5649

8473

11298

14122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1020

2040

3060

4080

5100

<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:

0.0537

AC:

8172

AN:

152184

Hom.:

334

Cov.:

AF XY:

0.0550

AC XY:

4091

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.110

AC:

4582

AN:

41502

American (AMR)

AF:

0.0386

AC:

590

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00836

AC:

AN:

3470

East Asian (EAS)

AF:

0.0428

AC:

221

AN:

5168

South Asian (SAS)

AF:

0.0427

AC:

206

AN:

4822

European-Finnish (FIN)

AF:

0.0671

AC:

712

AN:

10604

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0239

AC:

1623

AN:

68024

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

361

723

1084

1446

1807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

282

376

470

<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:

0.0323

Hom.:

432

Bravo

AF:

0.0551

EpiCase

AF:

0.0207

EpiControl

AF:

0.0192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

(source)

DANN

Benign

0.65

PhyloP100

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over