rs162887

Variant names:

• chr5-132293472-A-G
• rs162887
• ENST00000471826.1:n.138+1706T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132293472-A-G
• chr5-132293472-A-T

Variant summary

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

The ENST00000471826.1(P4HA2):​n.138+1706T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,142 control chromosomes in the GnomAD database, including 40,005 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 0.72 (40005 hom., cov: 33)
• Consequence: P4HA2 ENST00000471826.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 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.138+1706T>C		intron_variant	Intron 1 of 3	1
P4HA2	ENST00000431054.5	c.78+1706T>C		intron_variant	Intron 1 of 5	4		ENSP00000391257.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109145 AN: 152024 Hom.: 39957 Cov.: 33

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.869

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.718 AC: 109250 AN: 152142 Hom.: 40005 Cov.: 33 AF XY: 0.706 AC XY: 52479 AN XY: 74370

African (AFR) AF: 0.846 AC: 35152 AN: 41532

American (AMR) AF: 0.714 AC: 10930 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2430 AN: 3470

East Asian (EAS) AF: 0.620 AC: 3198 AN: 5160

South Asian (SAS) AF: 0.430 AC: 2073 AN: 4826

European-Finnish (FIN) AF: 0.572 AC: 6041 AN: 10564

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46940 AN: 67970

Other (OTH) AF: 0.717 AC: 1517 AN: 2116

Alfa AF: 0.698 Hom.: 4655

Bravo AF: 0.742

Asia WGS AF: 0.531 AC: 1847 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.55
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs162887; hg19: chr5-131629165;