rs11955347

Variant names:

• chr5-132232231-G-A
• rs11955347
• ENST00000431054.5:c.79-13587C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000431054.5(P4HA2):​c.79-13587C>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 ENST00000431054.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.599
• Publications: 34 publications found

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]

P4HA2 Gene-Disease associations (from GenCC):

• myopia

  Inheritance: AD Classification: STRONG Submitted by: G2P
• myopia 25, autosomal dominant

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000431054.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	P4HA2	ENST00000431054.5	TSL:4	c.79-13587C>T		intron	N/A	ENSP00000391257.1
	P4HA2	ENST00000439698.5	TSL:5	c.-18-13587C>T		intron	N/A	ENSP00000405406.1
	P4HA2	ENST00000416053.5	TSL:3	c.-18-13587C>T		intron	N/A	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

African (AFR) AF: 0.248 AC: 10277 AN: 41396

American (AMR) AF: 0.353 AC: 5391 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5180

South Asian (SAS) AF: 0.125 AC: 598 AN: 4802

European-Finnish (FIN) AF: 0.289 AC: 3041 AN: 10524

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30292 AN: 67934

Other (OTH) AF: 0.387 AC: 816 AN: 2108

Alfa AF: 0.413 Hom.: 33812

Bravo AF: 0.352

Asia WGS AF: 0.0840 AC: 293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.43
PhyloP100		-0.60

Splicing

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

Other links and lift over

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