chr4-94303661-T-G

Position:

• chr4-94303661-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000295256.10(HPGDS):​c.337-1417A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,022 control chromosomes in the GnomAD database, including 25,042 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 0.57 (25034 hom., cov: 32)
  • Exomes 𝑓: 0.48 (8 hom.)
• Consequence: HPGDS ENST00000295256.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.238

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.699 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HPGDS	NM_014485.3	c.337-1417A>C		intron_variant		ENST00000295256.10	NP_055300.1
HPGDS	XM_005262932.4	c.244-1417A>C		intron_variant			XP_005262989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HPGDS	ENST00000295256.10	c.337-1417A>C		intron_variant		1	NM_014485.3	ENSP00000295256	P1

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86826 AN: 151840 Hom.: 25011 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.613

Gnomad AMR AF: 0.640

Gnomad ASJ AF: 0.535

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.638

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.587

Gnomad OTH AF: 0.560

GnomAD4 exome AF: 0.484 AC: 31 AN: 64 Hom.: 8 AF XY: 0.463 AC XY: 25 AN XY: 54

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.625

Gnomad4 FIN exome AF: 0.583

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.572 AC: 86893 AN: 151958 Hom.: 25034 Cov.: 32 AF XY: 0.577 AC XY: 42862 AN XY: 74260

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.535

Gnomad4 EAS AF: 0.718

Gnomad4 SAS AF: 0.638

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.567

Alfa AF: 0.586 Hom.: 14995

Bravo AF: 0.574

Asia WGS AF: 0.680 AC: 2364 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.8
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs17021463; hg19: chr4-95224812;