Genetic Variant NM_014485.3:c.226+13T>C (chr4-94317860-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_014485.3(HPGDS):c.226+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,515,976 control chromosomes in the GnomAD database, including 68 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 0.011 ( 34 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 34 hom. )

Consequence

HPGDS
NM_014485.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.861

Publications

2 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=-0.83).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0115 (1746/152344) while in subpopulation AFR AF = 0.0395 (1642/41580). AF 95% confidence interval is 0.0379. There are 34 homozygotes in GnomAd4. There are 832 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPGDS	NM_014485.3 link	c.226+13T>C		intron_variant	Intron 3 of 5	ENST00000295256.10	NP_055300.1	O60760A0A384P5J0
HPGDS	XM_005262932.4 link	c.134-9117T>C		intron_variant	Intron 2 of 4		XP_005262989.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
HPGDS	ENST00000295256.10 link	c.226+13T>C	intron_variant	Intron 3 of 5	1	NM_014485.3	ENSP00000295256.5	O60760
ENSG00000287552	ENST00000667612.1 link	n.2375A>G	non_coding_transcript_exon_variant	Exon 1 of 2
HPGDS	ENST00000514774.1 link	n.306+13T>C	intron_variant	Intron 3 of 4	4

Frequencies

GnomAD3 genomes

AF:

0.0114

AC:

1742

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0395

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00445

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000961

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00717

GnomAD2 exomes

AF:

0.00335

AC:

830

AN:

248030

AF XY:

0.00227

show subpopulations

Gnomad AFR exome

AF:

0.0410

Gnomad AMR exome

AF:

0.00279

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000337

Gnomad OTH exome

AF:

0.00165

GnomAD4 exome

AF:

0.00133

AC:

1813

AN:

1363632

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

836

AN XY:

683906

show subpopulations

African (AFR)

AF:

0.0377

AC:

1184

AN:

31372

American (AMR)

AF:

0.00294

AC:

129

AN:

43830

Ashkenazi Jewish (ASJ)

AF:

0.0000784

AC:

AN:

25520

East Asian (EAS)

AF:

0.00182

AC:

AN:

39112

South Asian (SAS)

AF:

0.0000603

AC:

AN:

82898

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53056

Middle Eastern (MID)

AF:

0.00339

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.000244

AC:

250

AN:

1025052

Other (OTH)

AF:

0.00268

AC:

153

AN:

57192

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

160

240

320

400

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

176

220

<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:

0.0115

AC:

1746

AN:

152344

Hom.:

Cov.:

AF XY:

0.0112

AC XY:

832

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.0395

AC:

1642

AN:

41580

American (AMR)

AF:

0.00438

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000963

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000250

AC:

AN:

68032

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

179

268

358

447

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00548

Hom.:

Bravo

AF:

0.0131

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.3

(source)

DANN

Benign

0.70

PhyloP100

0.86

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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