Variant 4-94299483-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014485.3(HPGDS):c.597C>G(p.Leu199=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,609,488 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0028 ( 32 hom. )

Consequence

HPGDS
NM_014485.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.588

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 4-94299483-G-C is Benign according to our data. Variant chr4-94299483-G-C is described in ClinVar as [Benign]. Clinvar id is 790393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.588 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00283 (4118/1457470) while in subpopulation MID AF= 0.0414 (237/5730). AF 95% confidence interval is 0.037. There are 32 homozygotes in gnomad4_exome. There are 2134 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGDS	NM_014485.3 linkuse as main transcript	c.597C>G	p.Leu199=	synonymous_variant	6/6	ENST00000295256.10
HPGDS	XM_005262932.4 linkuse as main transcript	c.504C>G	p.Leu168=	synonymous_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGDS	ENST00000295256.10 linkuse as main transcript	c.597C>G	p.Leu199=	synonymous_variant	6/6	1	NM_014485.3	P1

Frequencies

GnomAD3 genomes

AF:

0.00352

AC:

534

AN:

151900

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00695

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00541

Gnomad FIN

AF:

0.00170

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.00318

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.00353

AC:

882

AN:

249948

Hom.:

AF XY:

0.00369

AC XY:

498

AN XY:

135102

show subpopulations

Gnomad AFR exome

AF:

0.00228

Gnomad AMR exome

AF:

0.00429

Gnomad ASJ exome

AF:

0.00664

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00444

Gnomad FIN exome

AF:

0.00255

Gnomad NFE exome

AF:

0.00346

Gnomad OTH exome

AF:

0.00839

GnomAD4 exome

AF:

0.00283

AC:

4118

AN:

1457470

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2134

AN XY:

724484

show subpopulations

Gnomad4 AFR exome

AF:

0.00285

Gnomad4 AMR exome

AF:

0.00484

Gnomad4 ASJ exome

AF:

0.00674

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00468

Gnomad4 FIN exome

AF:

0.00217

Gnomad4 NFE exome

AF:

0.00236

Gnomad4 OTH exome

AF:

0.00437

GnomAD4 genome

AF:

0.00351

AC:

533

AN:

152018

Hom.:

Cov.:

AF XY:

0.00375

AC XY:

279

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.00241

Gnomad4 AMR

AF:

0.00694

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00541

Gnomad4 FIN

AF:

0.00170

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00402

Hom.:

Bravo

AF:

0.00402

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

6.4

DANN

Benign

0.59

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over