rs2612656

Positions:

• chr4-174501138-G-A
• chr4-174501138-G-C

Variant summary

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

The NM_000860.6(HPGD):​c.422-5514C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.786 in 152,126 control chromosomes in the GnomAD database, including 47,196 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 0.79 (47196 hom., cov: 32)
• Consequence: HPGD NM_000860.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGD	NM_000860.6	c.422-5514C>T		intron_variant		ENST00000296522.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGD	ENST00000296522.11	c.422-5514C>T		intron_variant		1	NM_000860.6	P1

Frequencies

GnomAD3 genomes AF: 0.786 AC: 119474 AN: 152008 Hom.: 47150 Cov.: 32

Gnomad AFR AF: 0.810

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.740

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.822

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.840

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.782

Gnomad OTH AF: 0.783

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

GnomAD4 genome AF: 0.786 AC: 119577 AN: 152126 Hom.: 47196 Cov.: 32 AF XY: 0.785 AC XY: 58369 AN XY: 74356

Gnomad4 AFR AF: 0.810

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.822

Gnomad4 SAS AF: 0.623

Gnomad4 FIN AF: 0.840

Gnomad4 NFE AF: 0.782

Gnomad4 OTH AF: 0.778

Alfa AF: 0.777 Hom.: 77747

Bravo AF: 0.784

Asia WGS AF: 0.719 AC: 2503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.72

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: rs2612656; hg19: chr4-175422289;