dbSNP rs2059606: HPGDS:c.133+370C>T (chr4-94334127-G-A) – 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+370C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 161,982 control chromosomes in the GnomAD database, including 29,776 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 0.60 ( 27943 hom., cov: 32)

Exomes 𝑓: 0.60 ( 1833 hom. )

Consequence

HPGDS
NM_014485.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00400

Publications

5 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:):

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=-0.54).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPGDS	NM_014485.3 link	c.133+370C>T		intron_variant	Intron 2 of 5	ENST00000295256.10	NP_055300.1
HPGDS	XM_005262932.4 link	c.133+370C>T		intron_variant	Intron 2 of 4		XP_005262989.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
HPGDS	ENST00000295256.10 link	c.133+370C>T	intron_variant	Intron 2 of 5	1	NM_014485.3	ENSP00000295256.5
HPGDS	ENST00000514774.1 link	n.213+370C>T	intron_variant	Intron 2 of 4	4
ENSG00000287552	ENST00000667612.1 link	n.2871-8817G>A	intron_variant	Intron 1 of 1
HPGDS	ENST00000506331.1 link	n.*54C>T	downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91164

AN:

151872

Hom.:

27912

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.594

Gnomad AMR

AF:

0.522

Gnomad ASJ

AF:

0.623

Gnomad EAS

AF:

0.301

Gnomad SAS

AF:

0.445

Gnomad FIN

AF:

0.640

Gnomad MID

AF:

0.627

Gnomad NFE

AF:

0.631

Gnomad OTH

AF:

0.629

GnomAD4 exome

AF:

0.597

AC:

5965

AN:

9992

Hom.:

1833

AF XY:

0.598

AC XY:

3139

AN XY:

5252

show subpopulations

African (AFR)

AF:

0.679

AC:

163

AN:

240

American (AMR)

AF:

0.420

AC:

199

AN:

474

Ashkenazi Jewish (ASJ)

AF:

0.577

AC:

172

AN:

298

East Asian (EAS)

AF:

0.247

AC:

AN:

344

South Asian (SAS)

AF:

0.449

AC:

201

AN:

448

European-Finnish (FIN)

AF:

0.668

AC:

263

AN:

394

Middle Eastern (MID)

AF:

0.813

AC:

AN:

European-Non Finnish (NFE)

AF:

0.628

AC:

4530

AN:

7218

Other (OTH)

AF:

0.599

AC:

326

AN:

544

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

122

244

365

487

609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<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:

0.600

AC:

91233

AN:

151990

Hom.:

27943

Cov.:

AF XY:

0.594

AC XY:

44160

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.622

AC:

25779

AN:

41466

American (AMR)

AF:

0.521

AC:

7954

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.623

AC:

2163

AN:

3472

East Asian (EAS)

AF:

0.301

AC:

1558

AN:

5172

South Asian (SAS)

AF:

0.446

AC:

2144

AN:

4810

European-Finnish (FIN)

AF:

0.640

AC:

6755

AN:

10554

Middle Eastern (MID)

AF:

0.622

AC:

183

AN:

294

European-Non Finnish (NFE)

AF:

0.631

AC:

42847

AN:

67930

Other (OTH)

AF:

0.621

AC:

1312

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1868

3737

5605

7474

9342

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.605

Hom.:

20354

Bravo

AF:

0.590

Asia WGS

AF:

0.377

AC:

1311

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.92

PhyloP100

0.0040

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