Genetic Variant NM_014485.3:c.42A>G (chr4-94334588-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014485.3(HPGDS):c.42A>G(p.Arg14Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,613,338 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 25 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 104 hom. )

Consequence

HPGDS
NM_014485.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.29

Publications

3 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 -21 ACMG points.

BP4

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

BP6

Variant 4-94334588-T-C is Benign according to our data. Variant chr4-94334588-T-C is described in ClinVar as Benign. ClinVar VariationId is 771362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.29 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0571 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.42A>G	p.Arg14Arg	synonymous	Exon 2 of 6	NP_055300.1	A0A384P5J0

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HPGDS	ENST00000295256.10	TSL:1 MANE Select	c.42A>G	p.Arg14Arg	synonymous	Exon 2 of 6	ENSP00000295256.5	O60760
HPGDS	ENST00000944232.1		c.42A>G	p.Arg14Arg	synonymous	Exon 2 of 5	ENSP00000614291.1
HPGDS	ENST00000506331.1	TSL:3	n.133A>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.00549

AC:

836

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0468

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0119

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00909

GnomAD2 exomes

AF:

0.00951

AC:

2387

AN:

251056

AF XY:

0.00729

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0616

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00957

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000141

Gnomad OTH exome

AF:

0.00686

GnomAD4 exome

AF:

0.00230

AC:

3357

AN:

1461068

Hom.:

104

Cov.:

AF XY:

0.00201

AC XY:

1464

AN XY:

726862

show subpopulations

African (AFR)

AF:

0.000448

AC:

AN:

33452

American (AMR)

AF:

0.0590

AC:

2632

AN:

44640

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26104

East Asian (EAS)

AF:

0.00939

AC:

372

AN:

39608

South Asian (SAS)

AF:

0.00107

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000873

AC:

AN:

1111550

Other (OTH)

AF:

0.00239

AC:

144

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

148

295

443

590

738

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.00550

AC:

837

AN:

152270

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000554

AC:

AN:

41548

American (AMR)

AF:

0.0469

AC:

717

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.0117

AC:

AN:

5192

South Asian (SAS)

AF:

0.000829

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000191

AC:

AN:

68028

Other (OTH)

AF:

0.00900

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00286

Hom.:

Bravo

AF:

0.00820

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.2

(source)

DANN

Benign

0.70

PhyloP100

2.3

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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