rs4361509

Positions:

• chr5-132201060-G-A

Variant summary

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

The NM_001365677.2(P4HA2):​c.1252-2128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.343 in 152,202 control chromosomes in the GnomAD database, including 10,044 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 0.34 (10043 hom., cov: 33)
  • Exomes 𝑓: 1.0 (1 hom.)
• Consequence: P4HA2 NM_001365677.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
P4HA2	NM_001017974.2	c.1252-2128C>T		intron_variant		ENST00000360568.8	NP_001017974.1
P4HA2	NM_001365677.2	c.1252-2128C>T		intron_variant		ENST00000379104.7	NP_001352606.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
P4HA2	ENST00000360568.8	c.1252-2128C>T		intron_variant		1	NM_001017974.2	ENSP00000353772	A1
P4HA2	ENST00000379104.7	c.1252-2128C>T		intron_variant		1	NM_001365677.2	ENSP00000368398	P4
	ENST00000425667.1	n.1605G>A		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52269 AN: 152082 Hom.: 10043 Cov.: 33

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.595

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.355

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.381

GnomAD4 exome AF: 1.00 AC: 2 AN: 2 Hom.: 1 Cov.: 0 AF XY: 1.00 AC XY: 2 AN XY: 2

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.343 AC: 52273 AN: 152200 Hom.: 10043 Cov.: 33 AF XY: 0.334 AC XY: 24886 AN XY: 74410

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.355

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.376

Alfa AF: 0.350 Hom.: 1894

Bravo AF: 0.338

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs4361509; hg19: chr5-131536753; COSMIC: COSV51324177;