Variant chr10-73014217-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001017962.3(P4HA1):c.1368+7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00513 in 1,593,318 control chromosomes in the GnomAD database, including 331 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.026 ( 164 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 167 hom. )

Consequence

P4HA1
NM_001017962.3 splice_region, intron

Scores

Splicing: ADA: 0.0001145

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0380

Variant links:

Genes affected

P4HA1 (HGNC:8546): (prolyl 4-hydroxylase subunit alpha 1) 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]

P4HA1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 10-73014217-G-A is Benign according to our data. Variant chr10-73014217-G-A is described in ClinVar as [Benign]. Clinvar id is 784085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
P4HA1	NM_001017962.3 linkuse as main transcript	c.1368+7C>T	splice_region_variant, intron_variant	ENST00000394890.7
P4HA1	NM_000917.4 linkuse as main transcript	c.1368+7C>T	splice_region_variant, intron_variant
P4HA1	NM_001142595.2 linkuse as main transcript	c.1368+7C>T	splice_region_variant, intron_variant
P4HA1	NM_001142596.2 linkuse as main transcript	c.1314+7C>T	splice_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HA1	ENST00000394890.7 linkuse as main transcript	c.1368+7C>T		splice_region_variant, intron_variant		1	NM_001017962.3	A1	P13674-1

Frequencies

GnomAD3 genomes

AF:

0.0257

AC:

3904

AN:

152008

Hom.:

164

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0875

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00924

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.0148

GnomAD3 exomes

AF:

0.00748

AC:

1868

AN:

249594

Hom.:

AF XY:

0.00577

AC XY:

778

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.0906

Gnomad AMR exome

AF:

0.00419

Gnomad ASJ exome

AF:

0.0121

Gnomad EAS exome

AF:

0.00278

Gnomad SAS exome

AF:

0.000299

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000495

Gnomad OTH exome

AF:

0.00280

GnomAD4 exome

AF:

0.00296

AC:

4270

AN:

1441192

Hom.:

167

Cov.:

AF XY:

0.00259

AC XY:

1860

AN XY:

718182

show subpopulations

Gnomad4 AFR exome

AF:

0.0905

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.0120

Gnomad4 EAS exome

AF:

0.00172

Gnomad4 SAS exome

AF:

0.000211

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000288

Gnomad4 OTH exome

AF:

0.00617

GnomAD4 genome

AF:

0.0257

AC:

3905

AN:

152126

Hom.:

164

Cov.:

AF XY:

0.0248

AC XY:

1841

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0872

Gnomad4 AMR

AF:

0.00922

Gnomad4 ASJ

AF:

0.0170

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000618

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0146

Hom.:

Bravo

AF:

0.0290

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000654

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

7.7

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00011

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over