Genetic Variant NM_014485.3:c.337-1417A>C (chr4-94303661-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.337-1417A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,022 control chromosomes in the GnomAD database, including 25,042 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 0.57 ( 25034 hom., cov: 32)

Exomes 𝑓: 0.48 ( 8 hom. )

Consequence

HPGDS
NM_014485.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.238

Publications

26 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:

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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPGDS	NM_014485.3 link	c.337-1417A>C		intron_variant	Intron 4 of 5	ENST00000295256.10	NP_055300.1	O60760A0A384P5J0
HPGDS	XM_005262932.4 link	c.244-1417A>C		intron_variant	Intron 3 of 4		XP_005262989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPGDS	ENST00000295256.10 link	c.337-1417A>C		intron_variant	Intron 4 of 5	1	NM_014485.3	ENSP00000295256.5		O60760
HPGDS	ENST00000514774.1 link	n.*102A>C		downstream_gene_variant		4

Frequencies

GnomAD3 genomes

AF:

0.572

AC:

86826

AN:

151840

Hom.:

25011

Cov.:

show subpopulations

Gnomad AFR

AF:

0.499

Gnomad AMI

AF:

0.613

Gnomad AMR

AF:

0.640

Gnomad ASJ

AF:

0.535

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.638

Gnomad FIN

AF:

0.572

Gnomad MID

AF:

0.611

Gnomad NFE

AF:

0.587

Gnomad OTH

AF:

0.560

GnomAD4 exome

AF:

0.484

AC:

AN:

Hom.:

AF XY:

0.463

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.625

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.583

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.444

AC:

AN:

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.568

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.572

AC:

86893

AN:

151958

Hom.:

25034

Cov.:

AF XY:

0.577

AC XY:

42862

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.499

AC:

20671

AN:

41464

American (AMR)

AF:

0.641

AC:

9771

AN:

15238

Ashkenazi Jewish (ASJ)

AF:

0.535

AC:

1857

AN:

3468

East Asian (EAS)

AF:

0.718

AC:

3704

AN:

5158

South Asian (SAS)

AF:

0.638

AC:

3069

AN:

4812

European-Finnish (FIN)

AF:

0.572

AC:

6057

AN:

10582

Middle Eastern (MID)

AF:

0.602

AC:

177

AN:

294

European-Non Finnish (NFE)

AF:

0.586

AC:

39833

AN:

67922

Other (OTH)

AF:

0.567

AC:

1195

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1949

3898

5848

7797

9746

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

748

1496

2244

2992

3740

<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:

0.587

Hom.:

60957

Bravo

AF:

0.574

Asia WGS

AF:

0.680

AC:

2364

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.8

(source)

DANN

Benign

0.71

PhyloP100

0.24

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over