5-132233934-T-C

Variant summary

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

The ENST00000431054.5(P4HA2):c.79-15290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,128 control chromosomes in the GnomAD database, including 26,323 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 0.58 (26323 hom., cov: 33)
• Consequence: P4HA2 ENST00000431054.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 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	ENST00000416053.5	c.-18-15290A>G		intron_variant		3
P4HA2	ENST00000431054.5	c.79-15290A>G		intron_variant		4
P4HA2	ENST00000439698.5	c.-18-15290A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88666 AN: 152010 Hom.: 26304 Cov.: 33

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.900

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.583 AC: 88723 AN: 152128 Hom.: 26323 Cov.: 33 AF XY: 0.571 AC XY: 42437 AN XY: 74378

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.540

Gnomad4 ASJ AF: 0.623

Gnomad4 EAS AF: 0.524

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.477

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.592

Alfa AF: 0.590 Hom.: 5655

Bravo AF: 0.592

Asia WGS AF: 0.452 AC: 1574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.0
Dann	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs9791170; hg19: chr5-131569627;