Variant 4-94299521-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014485.3(HPGDS):c.559G>A(p.Val187Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0058 in 1,613,422 control chromosomes in the GnomAD database, including 133 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 49 hom., cov: 32)

Exomes 𝑓: 0.0046 ( 84 hom. )

Consequence

HPGDS
NM_014485.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.39

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00199157).

BP6

Variant 4-94299521-C-T is Benign according to our data. Variant chr4-94299521-C-T is described in ClinVar as [Benign]. Clinvar id is 790394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0172 (2609/151794) while in subpopulation AFR AF= 0.0484 (2000/41334). AF 95% confidence interval is 0.0466. There are 49 homozygotes in gnomad4. There are 1254 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGDS	NM_014485.3 linkuse as main transcript	c.559G>A	p.Val187Ile	missense_variant	6/6	ENST00000295256.10
HPGDS	XM_005262932.4 linkuse as main transcript	c.466G>A	p.Val156Ile	missense_variant	5/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGDS	ENST00000295256.10 linkuse as main transcript	c.559G>A	p.Val187Ile	missense_variant	6/6	1	NM_014485.3	P1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2602

AN:

151676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.0113

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.00561

Gnomad FIN

AF:

0.00180

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.00356

Gnomad OTH

AF:

0.0249

GnomAD3 exomes

AF:

0.00755

AC:

1897

AN:

251218

Hom.:

AF XY:

0.00667

AC XY:

905

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0487

Gnomad AMR exome

AF:

0.00775

Gnomad ASJ exome

AF:

0.0105

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00451

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00404

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.00462

AC:

6746

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00455

AC XY:

3308

AN XY:

727112

show subpopulations

Gnomad4 AFR exome

AF:

0.0516

Gnomad4 AMR exome

AF:

0.00872

Gnomad4 ASJ exome

AF:

0.0108

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.00480

Gnomad4 FIN exome

AF:

0.00221

Gnomad4 NFE exome

AF:

0.00271

Gnomad4 OTH exome

AF:

0.00878

GnomAD4 genome

AF:

0.0172

AC:

2609

AN:

151794

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1254

AN XY:

74188

show subpopulations

Gnomad4 AFR

AF:

0.0484

Gnomad4 AMR

AF:

0.0138

Gnomad4 ASJ

AF:

0.0113

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.00562

Gnomad4 FIN

AF:

0.00180

Gnomad4 NFE

AF:

0.00356

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.00597

Hom.:

Bravo

AF:

0.0193

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.0461

AC:

203

ESP6500EA

AF:

0.00547

AC:

ExAC

AF:

0.00834

AC:

1013

Asia WGS

AF:

0.00577

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 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.17

DEOGEN2

Benign

0.031

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Benign

0.81

REVEL

Benign

0.14

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.23

MVP

0.081

MPC

0.0089

ClinPred

0.013

GERP RS

5.7

Varity_R

0.046

gMVP

0.27

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