chr4-94315438-G-T

Variant names:

• chr4-94315438-G-T
• rs7658602
• NM_014485.3:c.226+2435C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014485.3(HPGDS):​c.226+2435C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 152,164 control chromosomes in the GnomAD database, including 571 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 0.071 (571 hom., cov: 33)
• Consequence: HPGDS NM_014485.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.591
• Publications: 5 publications found

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:58855):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014485.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPGDS	NM_014485.3	MANE Select	c.226+2435C>A		intron	N/A	NP_055300.1	A0A384P5J0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HPGDS	ENST00000295256.10	TSL:1 MANE Select	c.226+2435C>A		intron	N/A	ENSP00000295256.5	O60760
	HPGDS	ENST00000944232.1		c.134-6695C>A		intron	N/A	ENSP00000614291.1
	HPGDS	ENST00000514774.1	TSL:4	n.306+2435C>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0715 AC: 10866 AN: 152046 Hom.: 571 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.0597

Gnomad ASJ AF: 0.0568

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.0638

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0714 AC: 10865 AN: 152164 Hom.: 571 Cov.: 33 AF XY: 0.0717 AC XY: 5333 AN XY: 74406

African (AFR) AF: 0.0177 AC: 735 AN: 41512

American (AMR) AF: 0.0597 AC: 912 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0568 AC: 197 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.0209 AC: 101 AN: 4828

European-Finnish (FIN) AF: 0.119 AC: 1256 AN: 10562

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.109 AC: 7432 AN: 68004

Other (OTH) AF: 0.0631 AC: 133 AN: 2108

Alfa AF: 0.0744 Hom.: 258

Bravo AF: 0.0634

Asia WGS AF: 0.0140 AC: 48 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	8.9
DANN	Benign	0.67
PhyloP100		0.59
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7658602; hg19: chr4-95236589;