Variant 4-94334588-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_014485.3(HPGDS):c.42A>G(p.Arg14=) 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

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGDS	NM_014485.3 linkuse as main transcript	c.42A>G	p.Arg14=	synonymous_variant	2/6	ENST00000295256.10
HPGDS	XM_005262932.4 linkuse as main transcript	c.42A>G	p.Arg14=	synonymous_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
HPGDS	ENST00000295256.10 linkuse as main transcript	c.42A>G	p.Arg14=	synonymous_variant	2/6	1	NM_014485.3	P1
	ENST00000667612.1 linkuse as main transcript	n.2871-8356T>C		intron_variant, non_coding_transcript_variant
HPGDS	ENST00000506331.1 linkuse as main transcript	n.133A>G		non_coding_transcript_exon_variant	2/2	3
HPGDS	ENST00000514774.1 linkuse as main transcript	n.122A>G		non_coding_transcript_exon_variant	2/5	4

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

GnomAD3 exomes

AF:

0.00951

AC:

2387

AN:

251056

Hom.:

AF XY:

0.00729

AC XY:

989

AN XY:

135706

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 SAS exome

AF:

0.000851

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

Gnomad4 AFR exome

AF:

0.000448

Gnomad4 AMR exome

AF:

0.0590

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00939

Gnomad4 SAS exome

AF:

0.00107

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000873

Gnomad4 OTH exome

AF:

0.00239

GnomAD4 genome

AF:

0.00550

AC:

837

AN:

152270

Hom.:

Cov.:

AF XY:

0.00685

AC XY:

510

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.0469

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0117

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00900

Alfa

AF:

0.000977

Hom.:

Bravo

AF:

0.00820

Asia WGS

AF:

0.00866

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

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	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

9.2

DANN

Benign

0.70

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

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