rs157573

Variant names:

• chr5-132278745-A-C
• rs157573
• ENST00000471826.1:n.312-1257T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-132278745-A-C
• chr5-132278745-A-G

Variant summary

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

The ENST00000471826.1(P4HA2):​n.312-1257T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.813 in 152,186 control chromosomes in the GnomAD database, including 51,244 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 0.81 (51244 hom., cov: 32)
• Consequence: P4HA2 ENST00000471826.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.88
• Publications: 10 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 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	ENST00000471826.1	n.312-1257T>G		intron_variant	Intron 2 of 3	1
P4HA2	ENST00000431054.5	c.78+16433T>G		intron_variant	Intron 1 of 5	4		ENSP00000391257.1

Frequencies

GnomAD3 genomes AF: 0.813 AC: 123564 AN: 152066 Hom.: 51188 Cov.: 32

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.963

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.845

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.758

Gnomad NFE AF: 0.806

Gnomad OTH AF: 0.803

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

GnomAD4 genome AF: 0.813 AC: 123672 AN: 152186 Hom.: 51244 Cov.: 32 AF XY: 0.800 AC XY: 59551 AN XY: 74402

African (AFR) AF: 0.956 AC: 39737 AN: 41570

American (AMR) AF: 0.675 AC: 10317 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.845 AC: 2934 AN: 3472

East Asian (EAS) AF: 0.597 AC: 3064 AN: 5136

South Asian (SAS) AF: 0.655 AC: 3160 AN: 4824

European-Finnish (FIN) AF: 0.650 AC: 6889 AN: 10602

Middle Eastern (MID) AF: 0.776 AC: 228 AN: 294

European-Non Finnish (NFE) AF: 0.806 AC: 54766 AN: 67978

Other (OTH) AF: 0.804 AC: 1699 AN: 2112

Alfa AF: 0.803 Hom.: 40023

Bravo AF: 0.819

Asia WGS AF: 0.640 AC: 2228 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.062
DANN	Benign	0.31
PhyloP100		-4.9

Splicing

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

Other links and lift over

dbSNP: rs157573; hg19: chr5-131614438;