rs162887

chr5-132293472-A-Gchr5-132293472-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000471826.1(P4HA2):n.138+1706T>C variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA2	ENST00000471826.1	n.138+1706T>C		intron_variant, non_coding_transcript_variant		1
P4HA2	ENST00000431054.5	c.78+1706T>C		intron_variant		4

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

Gnomad4 AFR AF: 0.846

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.700

Gnomad4 EAS AF: 0.620

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.572

Gnomad4 NFE AF: 0.691

Gnomad4 OTH AF: 0.717

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs162887; hg19: chr5-131629165;