rs2059606

Variant names:

• chr4-94334127-G-A
• rs2059606
• NM_014485.3:c.133+370C>T

Variant summary

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

The NM_014485.3(HPGDS):​c.133+370C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 161,982 control chromosomes in the GnomAD database, including 29,776 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 0.60 (27943 hom., cov: 32)
  • Exomes 𝑓: 0.60 (1833 hom.)
• Consequence: HPGDS NM_014485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00400

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]

ENSG00000287552 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HPGDS	NM_014485.3	c.133+370C>T		intron_variant	Intron 2 of 5	ENST00000295256.10	NP_055300.1
HPGDS	XM_005262932.4	c.133+370C>T		intron_variant	Intron 2 of 4		XP_005262989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HPGDS	ENST00000295256.10	c.133+370C>T		intron_variant	Intron 2 of 5	1	NM_014485.3	ENSP00000295256.5
HPGDS	ENST00000514774.1	n.213+370C>T		intron_variant	Intron 2 of 4	4
ENSG00000287552	ENST00000667612.1	n.2871-8817G>A		intron_variant	Intron 1 of 1
HPGDS	ENST00000506331.1	n.*54C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91164 AN: 151872 Hom.: 27912 Cov.: 32

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.597 AC: 5965 AN: 9992 Hom.: 1833 AF XY: 0.598 AC XY: 3139 AN XY: 5252

Gnomad4 AFR exome AF: 0.679

Gnomad4 AMR exome AF: 0.420

Gnomad4 ASJ exome AF: 0.577

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.449

Gnomad4 FIN exome AF: 0.668

Gnomad4 NFE exome AF: 0.628

Gnomad4 OTH exome AF: 0.599

GnomAD4 genome AF: 0.600 AC: 91233 AN: 151990 Hom.: 27943 Cov.: 32 AF XY: 0.594 AC XY: 44160 AN XY: 74284

Gnomad4 AFR AF: 0.622

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.631

Gnomad4 OTH AF: 0.621

Alfa AF: 0.598 Hom.: 12393

Bravo AF: 0.590

Asia WGS AF: 0.377 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	10
DANN	Benign	0.92

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: rs2059606; hg19: chr4-95255278;