5-132233934-T-C

Variant names:

• chr5-132233934-T-C
• rs9791170
• ENST00000431054.5:c.79-15290A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 18 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=-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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
P4HA2	ENST00000431054.5	c.79-15290A>G		intron_variant	Intron 1 of 5	4		ENSP00000391257.1
P4HA2	ENST00000439698.5	c.-18-15290A>G		intron_variant	Intron 2 of 6	5		ENSP00000405406.1
P4HA2	ENST00000416053.5	c.-18-15290A>G		intron_variant	Intron 1 of 3	3		ENSP00000394953.1

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

African (AFR) AF: 0.566 AC: 23506 AN: 41496

American (AMR) AF: 0.540 AC: 8262 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2161 AN: 3468

East Asian (EAS) AF: 0.524 AC: 2709 AN: 5172

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4818

European-Finnish (FIN) AF: 0.477 AC: 5053 AN: 10586

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 43044 AN: 67984

Other (OTH) AF: 0.592 AC: 1251 AN: 2112

Alfa AF: 0.589 Hom.: 5773

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
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs9791170; hg19: chr5-131569627;