rs7705189

Variant names:

• chr5-132287665-A-G
• rs7705189
• ENST00000471826.1:n.139-6711T>C

Variant summary

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

The ENST00000471826.1(P4HA2):​n.139-6711T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 152,060 control chromosomes in the GnomAD database, including 11,362 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 0.37 (11362 hom., cov: 32)
• Consequence: P4HA2 ENST00000471826.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.330
• Publications: 24 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 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.139-6711T>C		intron_variant	Intron 1 of 3	1
P4HA2	ENST00000431054.5	c.78+7513T>C		intron_variant	Intron 1 of 5	4		ENSP00000391257.1

Frequencies

GnomAD3 genomes AF: 0.370 AC: 56228 AN: 151942 Hom.: 11360 Cov.: 32

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.368

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.370 AC: 56246 AN: 152060 Hom.: 11362 Cov.: 32 AF XY: 0.355 AC XY: 26396 AN XY: 74312

African (AFR) AF: 0.304 AC: 12594 AN: 41470

American (AMR) AF: 0.368 AC: 5622 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1675 AN: 3472

East Asian (EAS) AF: 0.00290 AC: 15 AN: 5180

South Asian (SAS) AF: 0.139 AC: 671 AN: 4824

European-Finnish (FIN) AF: 0.296 AC: 3124 AN: 10562

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30919 AN: 67946

Other (OTH) AF: 0.414 AC: 877 AN: 2116

Alfa AF: 0.384 Hom.: 1814

Bravo AF: 0.378

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.80
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs7705189; hg19: chr5-131623358;