rs11955347

Positions:

• chr5-132232231-G-A

Variant summary

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

The ENST00000416053.5(P4HA2):​c.-18-13587C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 151,874 control chromosomes in the GnomAD database, including 10,284 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 0.35 (10284 hom., cov: 31)
• Consequence: P4HA2 ENST00000416053.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.132232231G>A		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P4HA2	ENST00000431054.5	c.79-13587C>T		intron_variant		4		ENSP00000391257.1
P4HA2	ENST00000439698.5	c.-18-13587C>T		intron_variant		5		ENSP00000405406.1
P4HA2	ENST00000416053.5	c.-18-13587C>T		intron_variant		3		ENSP00000394953.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52750 AN: 151756 Hom.: 10283 Cov.: 31

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.687

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.347 AC: 52758 AN: 151874 Hom.: 10284 Cov.: 31 AF XY: 0.333 AC XY: 24756 AN XY: 74236

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.00328

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.387

Alfa AF: 0.432 Hom.: 22977

Bravo AF: 0.352

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.43

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11955347; hg19: chr5-131567924; COSMIC: COSV51324239;