rs7349744

chr4-174503021-G-Achr4-174503021-G-T

Variant summary

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

The NM_000860.6(HPGD):c.421+5675C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.244 in 152,104 control chromosomes in the GnomAD database, including 5,309 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 0.24 (5309 hom., cov: 32)
• Consequence: HPGD NM_000860.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.787

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HPGD	NM_000860.6	c.421+5675C>T		intron_variant		ENST00000296522.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HPGD	ENST00000296522.11	c.421+5675C>T		intron_variant		1	NM_000860.6	P1

Frequencies

GnomAD3 genomes AF: 0.244 AC: 37104 AN: 151986 Hom.: 5304 Cov.: 32

Gnomad AFR AF: 0.0983

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.244 AC: 37121 AN: 152104 Hom.: 5309 Cov.: 32 AF XY: 0.249 AC XY: 18540 AN XY: 74334

Gnomad4 AFR AF: 0.0983

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.299

Gnomad4 SAS AF: 0.293

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.269

Alfa AF: 0.293 Hom.: 7061

Bravo AF: 0.230

Asia WGS AF: 0.303 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.33
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: rs7349744; hg19: chr4-175424172;