rs7627711

chr3-190055228-C-T

Variant summary

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

The NM_018192.4(P3H2):c.481-59786G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 151,992 control chromosomes in the GnomAD database, including 13,299 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 0.40 (13299 hom., cov: 32)
• Consequence: P3H2 NM_018192.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0510

Genes affected

P3H2 (HGNC:19317): (prolyl 3-hydroxylase 2) This gene encodes a member of the prolyl 3-hydroxylase subfamily of 2-oxo-glutarate-dependent dioxygenases. These enzymes play a critical role in collagen chain assembly, stability and cross-linking by catalyzing post-translational 3-hydroxylation of proline residues. Mutations in this gene are associated with nonsyndromic severe myopia with cataract and vitreoretinal degeneration, and downregulation of this gene may play a role in breast cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P3H2	NM_018192.4	c.481-59786G>A		intron_variant		ENST00000319332.10
P3H2	NM_001134418.2	c.-63-59786G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P3H2	ENST00000319332.10	c.481-59786G>A		intron_variant		1	NM_018192.4	P1
P3H2	ENST00000427335.6	c.-63-59786G>A		intron_variant		1
P3H2	ENST00000426003.1	c.-63-59786G>A		intron_variant		4
P3H2	ENST00000444866.5	c.-63-59786G>A		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.399 AC: 60666 AN: 151874 Hom.: 13258 Cov.: 32

Gnomad AFR AF: 0.604

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.280

Gnomad ASJ AF: 0.370

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.400 AC: 60767 AN: 151992 Hom.: 13299 Cov.: 32 AF XY: 0.396 AC XY: 29442 AN XY: 74284

Gnomad4 AFR AF: 0.604

Gnomad4 AMR AF: 0.280

Gnomad4 ASJ AF: 0.370

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.292

Gnomad4 FIN AF: 0.294

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.385

Alfa AF: 0.344 Hom.: 5061

Bravo AF: 0.409

Asia WGS AF: 0.310 AC: 1083 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.3
Dann	Benign	0.56

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: rs7627711; hg19: chr3-189773017;