Genetic Variant HPGDS:c.133+11A>C (chr4-94334486-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014485.3(HPGDS):c.133+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,565,838 control chromosomes in the GnomAD database, including 298,264 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 0.64 ( 32272 hom., cov: 32)

Exomes 𝑓: 0.61 ( 265992 hom. )

Consequence

HPGDS
NM_014485.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.547

Publications

12 publications found

Variant links:

Genes affected

HPGDS (HGNC:17890): (hematopoietic prostaglandin D synthase) Prostaglandin-D synthase is a sigma class glutathione-S-transferase family member. The enzyme catalyzes the conversion of PGH2 to PGD2 and plays a role in the production of prostanoids in the immune system and mast cells. The presence of this enzyme can be used to identify the differentiation stage of human megakaryocytes. [provided by RefSeq, Jul 2008]

HPGDS links:

ENSG00000287552 (HGNC:58855):

ENSG00000287552 links:

Genome browser will be placed here

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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014485.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPGDS	NM_014485.3	MANE Select	c.133+11A>C		intron	N/A	NP_055300.1	A0A384P5J0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
HPGDS	ENST00000295256.10	TSL:1 MANE Select	c.133+11A>C	intron	N/A	ENSP00000295256.5	O60760
HPGDS	ENST00000944232.1		c.133+11A>C	intron	N/A	ENSP00000614291.1
HPGDS	ENST00000506331.1	TSL:3	n.235A>C	non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.642

AC:

97481

AN:

151880

Hom.:

32225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.765

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.536

Gnomad ASJ

AF:

0.628

Gnomad EAS

AF:

0.303

Gnomad SAS

AF:

0.447

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.649

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.660

GnomAD2 exomes

AF:

0.569

AC:

126659

AN:

222540

AF XY:

0.569

show subpopulations

Gnomad AFR exome

AF:

0.775

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.617

Gnomad EAS exome

AF:

0.310

Gnomad FIN exome

AF:

0.638

Gnomad NFE exome

AF:

0.631

Gnomad OTH exome

AF:

0.604

GnomAD4 exome

AF:

0.607

AC:

857760

AN:

1413840

Hom.:

265992

Cov.:

AF XY:

0.603

AC XY:

422659

AN XY:

701212

show subpopulations

African (AFR)

AF:

0.781

AC:

24421

AN:

31276

American (AMR)

AF:

0.412

AC:

14980

AN:

36368

Ashkenazi Jewish (ASJ)

AF:

0.615

AC:

15124

AN:

24574

East Asian (EAS)

AF:

0.260

AC:

9984

AN:

38366

South Asian (SAS)

AF:

0.458

AC:

35496

AN:

77466

European-Finnish (FIN)

AF:

0.640

AC:

33610

AN:

52504

Middle Eastern (MID)

AF:

0.656

AC:

3638

AN:

5544

European-Non Finnish (NFE)

AF:

0.629

AC:

684738

AN:

1089428

Other (OTH)

AF:

0.613

AC:

35769

AN:

58314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

14831

29662

44492

59323

74154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18286

36572

54858

73144

91430

<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:

0.642

AC:

97567

AN:

151998

Hom.:

32272

Cov.:

AF XY:

0.635

AC XY:

47134

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.766

AC:

31727

AN:

41430

American (AMR)

AF:

0.535

AC:

8173

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.628

AC:

2179

AN:

3472

East Asian (EAS)

AF:

0.303

AC:

1569

AN:

5172

South Asian (SAS)

AF:

0.448

AC:

2164

AN:

4830

European-Finnish (FIN)

AF:

0.640

AC:

6750

AN:

10548

Middle Eastern (MID)

AF:

0.646

AC:

190

AN:

294

European-Non Finnish (NFE)

AF:

0.631

AC:

42898

AN:

67950

Other (OTH)

AF:

0.652

AC:

1378

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1728

3457

5185

6914

8642

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

778

1556

2334

3112

3890

<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:

0.625

Hom.:

116327

Bravo

AF:

0.637

Asia WGS

AF:

0.385

AC:

1336

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.8

(source)

DANN

Benign

0.67

PhyloP100

-0.55

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over