Variant chr17-81844101-C-T 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_000918.4(P4HB):c.1447-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0211 in 1,598,586 control chromosomes in the GnomAD database, including 2,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 533 hom., cov: 33)

Exomes 𝑓: 0.018 ( 1594 hom. )

Consequence

P4HB
NM_000918.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002609

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -5.67

Variant links:

Genes affected

P4HB (HGNC:8548): (prolyl 4-hydroxylase subunit beta) This gene encodes the beta subunit of prolyl 4-hydroxylase, a highly abundant multifunctional enzyme that belongs to the protein disulfide isomerase family. When present as a tetramer consisting of two alpha and two beta subunits, this enzyme is involved in hydroxylation of prolyl residues in preprocollagen. This enzyme is also a disulfide isomerase containing two thioredoxin domains that catalyze the formation, breakage and rearrangement of disulfide bonds. Other known functions include its ability to act as a chaperone that inhibits aggregation of misfolded proteins in a concentration-dependent manner, its ability to bind thyroid hormone, its role in both the influx and efflux of S-nitrosothiol-bound nitric oxide, and its function as a subunit of the microsomal triglyceride transfer protein complex. [provided by RefSeq, Jul 2008]

P4HB 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=-0.78).

BP6

Variant 17-81844101-C-T is Benign according to our data. Variant chr17-81844101-C-T is described in ClinVar as [Benign]. Clinvar id is 1269426.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
P4HB	NM_000918.4 linkuse as main transcript	c.1447-9G>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000331483.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
P4HB	ENST00000331483.9 linkuse as main transcript	c.1447-9G>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000918.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0545

AC:

8287

AN:

152194

Hom.:

533

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0856

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.175

Gnomad SAS

AF:

0.0459

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00317

Gnomad OTH

AF:

0.0416

GnomAD3 exomes

AF:

0.0471

AC:

11832

AN:

251314

Hom.:

838

AF XY:

0.0409

AC XY:

5559

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.136

Gnomad AMR exome

AF:

0.125

Gnomad ASJ exome

AF:

0.00754

Gnomad EAS exome

AF:

0.179

Gnomad SAS exome

AF:

0.0394

Gnomad FIN exome

AF:

0.00490

Gnomad NFE exome

AF:

0.00383

Gnomad OTH exome

AF:

0.0277

GnomAD4 exome

AF:

0.0175

AC:

25373

AN:

1446274

Hom.:

1594

Cov.:

AF XY:

0.0172

AC XY:

12406

AN XY:

720516

show subpopulations

Gnomad4 AFR exome

AF:

0.139

Gnomad4 AMR exome

AF:

0.117

Gnomad4 ASJ exome

AF:

0.00699

Gnomad4 EAS exome

AF:

0.189

Gnomad4 SAS exome

AF:

0.0384

Gnomad4 FIN exome

AF:

0.00551

Gnomad4 NFE exome

AF:

0.00242

Gnomad4 OTH exome

AF:

0.0246

GnomAD4 genome

AF:

0.0545

AC:

8298

AN:

152312

Hom.:

533

Cov.:

AF XY:

0.0559

AC XY:

4165

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.132

Gnomad4 AMR

AF:

0.0856

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.175

Gnomad4 SAS

AF:

0.0461

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.00318

Gnomad4 OTH

AF:

0.0407

Alfa

AF:

0.0228

Hom.:

Bravo

AF:

0.0648

Asia WGS

AF:

0.0910

AC:

315

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2018	- -
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

-0.78

CADD

Benign

0.77

DANN

Benign

0.88

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00026

dbscSNV1_RF

Benign

0.010

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