Genetic Variant DHRSX:c.286+4C>G (chrX-2408741-G-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_145177.3(DHRSX):c.286+4C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,606,450 control chromosomes in the GnomAD database, including 41,220 homozygotes. There are 168,329 hemizygotes in GnomAD. 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 0.30 ( 8481 hom., 21702 hem., cov: 31)

Exomes 𝑓: 0.20 ( 32739 hom. 146627 hem. )

Consequence

DHRSX
NM_145177.3 splice_region, intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.30

Publications

0 publications found

Variant links:

Genes affected

DHRSX (HGNC:18399): (dehydrogenase/reductase X-linked) Predicted to enable oxidoreductase activity. Involved in positive regulation of autophagy. Located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

DHRSX links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145177.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRSX	NM_145177.3	MANE Select	c.286+4C>G		splice_region intron	N/A	NP_660160.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
DHRSX	ENST00000334651.11	TSL:1 MANE Select	c.286+4C>G	splice_region intron	N/A	ENSP00000334113.5
DHRSX	ENST00000412516.7	TSL:2	c.217+16456C>G	intron	N/A	ENSP00000391778.2
DHRSX	ENST00000444280.6	TSL:2	c.85+4C>G	splice_region intron	N/A	ENSP00000402741.1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44700

AN:

151328

Hom.:

8462

Cov.:

show subpopulations

Gnomad AFR

AF:

0.535

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.345

Gnomad EAS

AF:

0.199

Gnomad SAS

AF:

0.270

Gnomad FIN

AF:

0.238

Gnomad MID

AF:

0.322

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.299

GnomAD2 exomes

AF:

0.232

AC:

56918

AN:

245566

AF XY:

0.230

show subpopulations

Gnomad AFR exome

AF:

0.540

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.358

Gnomad EAS exome

AF:

0.207

Gnomad FIN exome

AF:

0.220

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.199

AC:

289532

AN:

1455018

Hom.:

32739

Cov.:

AF XY:

0.203

AC XY:

146627

AN XY:

723470

show subpopulations

African (AFR)

AF:

0.548

AC:

18120

AN:

33040

American (AMR)

AF:

0.201

AC:

8822

AN:

43844

Ashkenazi Jewish (ASJ)

AF:

0.350

AC:

9085

AN:

25958

East Asian (EAS)

AF:

0.186

AC:

7365

AN:

39638

South Asian (SAS)

AF:

0.276

AC:

23437

AN:

84874

European-Finnish (FIN)

AF:

0.210

AC:

11191

AN:

53244

Middle Eastern (MID)

AF:

0.347

AC:

1982

AN:

5720

European-Non Finnish (NFE)

AF:

0.177

AC:

195743

AN:

1108616

Other (OTH)

AF:

0.229

AC:

13787

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

9716

19432

29147

38863

48579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7066

14132

21198

28264

35330

<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:

0.296

AC:

44753

AN:

151432

Hom.:

8481

Cov.:

AF XY:

0.294

AC XY:

21702

AN XY:

73912

show subpopulations

African (AFR)

AF:

0.535

AC:

22102

AN:

41300

American (AMR)

AF:

0.224

AC:

3411

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.345

AC:

1194

AN:

3464

East Asian (EAS)

AF:

0.198

AC:

1023

AN:

5162

South Asian (SAS)

AF:

0.269

AC:

1292

AN:

4800

European-Finnish (FIN)

AF:

0.238

AC:

2462

AN:

10326

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12299

AN:

67864

Other (OTH)

AF:

0.303

AC:

640

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

1381

2761

4142

5522

6903

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

422

844

1266

1688

2110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Bravo

AF:

0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.023

(source)

DANN

Benign

0.31

PhyloP100

-2.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.25

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.25

Position offset: 4

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