rs4594848

chr5-132250905-C-A

Variant summary

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

The ENST00000471826.1(P4HA2):n.510G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,092 control chromosomes in the GnomAD database, including 9,818 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 0.33 (9816 hom., cov: 32)
  • Exomes 𝑓: 0.70 (2 hom.)
• Consequence: P4HA2 ENST00000471826.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.182

Genes affected

P4HA2 (HGNC:8547): (prolyl 4-hydroxylase subunit alpha 2) This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA2	ENST00000471826.1	n.510G>T		non_coding_transcript_exon_variant	4/4	1
P4HA2	ENST00000416053.5	c.-19+26437G>T		intron_variant		3
P4HA2	ENST00000431054.5	c.79-32261G>T		intron_variant		4
P4HA2	ENST00000439698.5	c.-19+26437G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50654 AN: 151964 Hom.: 9813 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.688

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.386

GnomAD4 exome AF: 0.700 AC: 7 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.333 AC: 50670 AN: 152082 Hom.: 9816 Cov.: 32 AF XY: 0.320 AC XY: 23751 AN XY: 74320

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.474

Gnomad4 EAS AF: 0.00308

Gnomad4 SAS AF: 0.126

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.445

Gnomad4 OTH AF: 0.381

Alfa AF: 0.399 Hom.: 6158

Bravo AF: 0.336

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.3
Dann	Benign	0.65

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4594848; hg19: chr5-131586598;