5-132286608-A-T

Variant names:

• chr5-132286608-A-T
• rs381870
• ENST00000471826.1:n.139-5654T>A

Variant summary

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

The ENST00000471826.1(P4HA2):​n.139-5654T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,176 control chromosomes in the GnomAD database, including 3,597 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 0.21 (3597 hom., cov: 33)
• Consequence: P4HA2 ENST00000471826.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.755
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.508 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.139-5654T>A		intron_variant	Intron 1 of 3	1
P4HA2	ENST00000431054.5	c.78+8570T>A		intron_variant	Intron 1 of 5	4		ENSP00000391257.1

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31639 AN: 152058 Hom.: 3592 Cov.: 33

Gnomad AFR AF: 0.207

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.526

Gnomad SAS AF: 0.249

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.187

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

GnomAD4 genome AF: 0.208 AC: 31680 AN: 152176 Hom.: 3597 Cov.: 33 AF XY: 0.211 AC XY: 15691 AN XY: 74412

African (AFR) AF: 0.207 AC: 8612 AN: 41518

American (AMR) AF: 0.173 AC: 2652 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 616 AN: 3472

East Asian (EAS) AF: 0.525 AC: 2715 AN: 5174

South Asian (SAS) AF: 0.249 AC: 1203 AN: 4824

European-Finnish (FIN) AF: 0.194 AC: 2052 AN: 10596

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13190 AN: 67976

Other (OTH) AF: 0.195 AC: 411 AN: 2112

Alfa AF: 0.207 Hom.: 411

Bravo AF: 0.206

Asia WGS AF: 0.364 AC: 1267 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.2
DANN	Benign	0.49
PhyloP100		-0.76

Splicing

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

Other links and lift over

dbSNP: rs381870; hg19: chr5-131622301;