rs17360144

chr4-174501850-A-C

Variant summary

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

The NM_000860.6(HPGD):c.422-6226T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0593 in 152,232 control chromosomes in the GnomAD database, including 456 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 0.059 (456 hom., cov: 33)
• Consequence: HPGD NM_000860.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160

Genes affected

HPGD (HGNC:5154): (15-hydroxyprostaglandin dehydrogenase) This gene encodes a member of the short-chain nonmetalloenzyme alcohol dehydrogenase protein family. The encoded enzyme is responsible for the metabolism of prostaglandins, which function in a variety of physiologic and cellular processes such as inflammation. Mutations in this gene result in primary autosomal recessive hypertrophic osteoarthropathy and cranioosteoarthropathy. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.129 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGD	NM_000860.6	c.422-6226T>G		intron_variant		ENST00000296522.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGD	ENST00000296522.11	c.422-6226T>G		intron_variant		1	NM_000860.6	P1

Frequencies

GnomAD3 genomes AF: 0.0593 AC: 9021 AN: 152114 Hom.: 454 Cov.: 33

Gnomad AFR AF: 0.0145

Gnomad AMI AF: 0.0603

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.0850

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0705

Gnomad OTH AF: 0.0516

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

GnomAD4 genome AF: 0.0593 AC: 9027 AN: 152232 Hom.: 456 Cov.: 33 AF XY: 0.0610 AC XY: 4539 AN XY: 74432

Gnomad4 AFR AF: 0.0144

Gnomad4 AMR AF: 0.134

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0804

Gnomad4 FIN AF: 0.0850

Gnomad4 NFE AF: 0.0705

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0740 Hom.: 259

Bravo AF: 0.0610

Asia WGS AF: 0.0290 AC: 99 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	4.7
Dann	Benign	0.80

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: rs17360144; hg19: chr4-175423001;