dbSNP rs4594848: P4HA2:n.510G>T (chr5-132250905-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000471826.1(P4HA2):n.510G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,092 control chromosomes in the GnomAD database, including 9,818 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 0.33 ( 9816 hom., cov: 32)

Exomes 𝑓: 0.70 ( 2 hom. )

Consequence

P4HA2
ENST00000471826.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.182

Publications

21 publications found

Variant links:

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

P4HA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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 = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
P4HA2	ENST00000471826.1 link	n.510G>T	non_coding_transcript_exon_variant	Exon 4 of 4	1
P4HA2	ENST00000431054.5 link	c.79-32261G>T	intron_variant	Intron 1 of 5	4	ENSP00000391257.1	E7EPI9
P4HA2	ENST00000439698.5 link	c.-19+26437G>T	intron_variant	Intron 2 of 6	5	ENSP00000405406.1	E7ERI1
P4HA2	ENST00000416053.5 link	c.-19+26437G>T	intron_variant	Intron 1 of 3	3	ENSP00000394953.1	C9JN43

Frequencies

GnomAD3 genomes

AF:

0.333

AC:

50654

AN:

151964

Hom.:

9813

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.688

Gnomad AMR

AF:

0.349

Gnomad ASJ

AF:

0.474

Gnomad EAS

AF:

0.00308

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.405

Gnomad NFE

AF:

0.445

Gnomad OTH

AF:

0.386

GnomAD4 exome

AF:

0.700

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

1.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.667

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.642

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.333

AC:

50670

AN:

152082

Hom.:

9816

Cov.:

AF XY:

0.320

AC XY:

23751

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.198

AC:

8228

AN:

41478

American (AMR)

AF:

0.348

AC:

5325

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.474

AC:

1644

AN:

3468

East Asian (EAS)

AF:

0.00308

AC:

AN:

5190

South Asian (SAS)

AF:

0.126

AC:

607

AN:

4816

European-Finnish (FIN)

AF:

0.286

AC:

3023

AN:

10552

Middle Eastern (MID)

AF:

0.408

AC:

120

AN:

294

European-Non Finnish (NFE)

AF:

0.445

AC:

30276

AN:

67970

Other (OTH)

AF:

0.381

AC:

804

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1591

3182

4772

6363

7954

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

472

944

1416

1888

2360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.402

Hom.:

6911

Bravo

AF:

0.336

Asia WGS

AF:

0.0850

AC:

294

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

(source)

DANN

Benign

0.65

PhyloP100

-0.18

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over