4-94334486-T-G

Position:

• chr4-94334486-T-G

Variant summary

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

The NM_014485.3(HPGDS):​c.133+11A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,565,838 control chromosomes in the GnomAD database, including 298,264 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 0.64 (32272 hom., cov: 32)
  • Exomes 𝑓: 0.61 (265992 hom.)
• Consequence: HPGDS NM_014485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGDS	NM_014485.3	c.133+11A>C		intron_variant		ENST00000295256.10
HPGDS	XM_005262932.4	c.133+11A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGDS	ENST00000295256.10	c.133+11A>C		intron_variant		1	NM_014485.3	P1
	ENST00000667612.1	n.2871-8458T>G		intron_variant, non_coding_transcript_variant
HPGDS	ENST00000506331.1	n.235A>C		non_coding_transcript_exon_variant	2/2	3
HPGDS	ENST00000514774.1	n.213+11A>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.642 AC: 97481 AN: 151880 Hom.: 32225 Cov.: 32

Gnomad AFR AF: 0.765

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.628

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.660

GnomAD3 exomes AF: 0.569 AC: 126659 AN: 222540 Hom.: 37999 AF XY: 0.569 AC XY: 68649 AN XY: 120558

Gnomad AFR exome AF: 0.775

Gnomad AMR exome AF: 0.395

Gnomad ASJ exome AF: 0.617

Gnomad EAS exome AF: 0.310

Gnomad SAS exome AF: 0.458

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.631

Gnomad OTH exome AF: 0.604

GnomAD4 exome AF: 0.607 AC: 857760 AN: 1413840 Hom.: 265992 Cov.: 29 AF XY: 0.603 AC XY: 422659 AN XY: 701212

Gnomad4 AFR exome AF: 0.781

Gnomad4 AMR exome AF: 0.412

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.260

Gnomad4 SAS exome AF: 0.458

Gnomad4 FIN exome AF: 0.640

Gnomad4 NFE exome AF: 0.629

Gnomad4 OTH exome AF: 0.613

GnomAD4 genome AF: 0.642 AC: 97567 AN: 151998 Hom.: 32272 Cov.: 32 AF XY: 0.635 AC XY: 47134 AN XY: 74282

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.535

Gnomad4 ASJ AF: 0.628

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.448

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.652

Alfa AF: 0.623 Hom.: 51902

Bravo AF: 0.637

Asia WGS AF: 0.385 AC: 1336 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.8
DANN	Benign	0.67

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: rs2289186; hg19: chr4-95255637; COSMIC: COSV54773440;