rs55672062

Positions:

• chr4-94317860-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_014485.3(HPGDS):​c.226+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,515,976 control chromosomes in the GnomAD database, including 68 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 0.011 (34 hom., cov: 32)
  • Exomes 𝑓: 0.0013 (34 hom.)
• Consequence: HPGDS NM_014485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.861

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=-0.83).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0115 (1746/152344) while in subpopulation AFR AF= 0.0395 (1642/41580). AF 95% confidence interval is 0.0379. There are 34 homozygotes in gnomad4. There are 832 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 34 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGDS	NM_014485.3	c.226+13T>C		intron_variant		ENST00000295256.10
HPGDS	XM_005262932.4	c.134-9117T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGDS	ENST00000295256.10	c.226+13T>C		intron_variant		1	NM_014485.3	P1
	ENST00000667612.1	n.2375A>G		non_coding_transcript_exon_variant	1/2
HPGDS	ENST00000514774.1	n.306+13T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0114 AC: 1742 AN: 152226 Hom.: 34 Cov.: 32

Gnomad AFR AF: 0.0395

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00717

GnomAD3 exomes AF: 0.00335 AC: 830 AN: 248030 Hom.: 14 AF XY: 0.00227 AC XY: 304 AN XY: 134018

Gnomad AFR exome AF: 0.0410

Gnomad AMR exome AF: 0.00279

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00131

Gnomad SAS exome AF: 0.0000337

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000337

Gnomad OTH exome AF: 0.00165

GnomAD4 exome AF: 0.00133 AC: 1813 AN: 1363632 Hom.: 34 Cov.: 22 AF XY: 0.00122 AC XY: 836 AN XY: 683906

Gnomad4 AFR exome AF: 0.0377

Gnomad4 AMR exome AF: 0.00294

Gnomad4 ASJ exome AF: 0.0000784

Gnomad4 EAS exome AF: 0.00182

Gnomad4 SAS exome AF: 0.0000603

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000244

Gnomad4 OTH exome AF: 0.00268

GnomAD4 genome AF: 0.0115 AC: 1746 AN: 152344 Hom.: 34 Cov.: 32 AF XY: 0.0112 AC XY: 832 AN XY: 74486

Gnomad4 AFR AF: 0.0395

Gnomad4 AMR AF: 0.00438

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00548 Hom.: 4

Bravo AF: 0.0131

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.3
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs55672062; hg19: chr4-95239011;