rs7529452

Positions:

chr1-11949898-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000302.4(PLOD1):c.294C>T(p.Phe98=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 1,613,408 control chromosomes in the GnomAD database, including 82,689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6299 hom., cov: 32)

Exomes 𝑓: 0.32 ( 76390 hom. )

Consequence

PLOD1
NM_000302.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.08

Variant links:

Genes affected

PLOD1 (HGNC:9081): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1) Lysyl hydroxylase is a membrane-bound homodimeric protein localized to the cisternae of the endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VI have deficiencies in lysyl hydroxylase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PLOD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 1-11949898-C-T is Benign according to our data. Variant chr1-11949898-C-T is described in ClinVar as [Benign]. Clinvar id is 255803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11949898-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLOD1	NM_000302.4 linkuse as main transcript	c.294C>T	p.Phe98=	synonymous_variant	3/19	ENST00000196061.5	NP_000293.2
PLOD1	NM_001316320.2 linkuse as main transcript	c.435C>T	p.Phe145=	synonymous_variant	4/20		NP_001303249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLOD1	ENST00000196061.5 linkuse as main transcript	c.294C>T	p.Phe98=	synonymous_variant	3/19	1	NM_000302.4	ENSP00000196061	P1	Q02809-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38595

AN:

151958

Hom.:

6298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0637

Gnomad AMI

AF:

0.138

Gnomad AMR

AF:

0.289

Gnomad ASJ

AF:

0.215

Gnomad EAS

AF:

0.378

Gnomad SAS

AF:

0.432

Gnomad FIN

AF:

0.437

Gnomad MID

AF:

0.253

Gnomad NFE

AF:

0.315

Gnomad OTH

AF:

0.274

GnomAD3 exomes

AF:

0.329

AC:

82814

AN:

251354

Hom.:

14831

AF XY:

0.336

AC XY:

45707

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.0589

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.424

Gnomad FIN exome

AF:

0.446

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.331

GnomAD4 exome

AF:

0.317

AC:

463265

AN:

1461332

Hom.:

76390

Cov.:

AF XY:

0.321

AC XY:

233607

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.0541

Gnomad4 AMR exome

AF:

0.351

Gnomad4 ASJ exome

AF:

0.220

Gnomad4 EAS exome

AF:

0.343

Gnomad4 SAS exome

AF:

0.428

Gnomad4 FIN exome

AF:

0.446

Gnomad4 NFE exome

AF:

0.311

Gnomad4 OTH exome

AF:

0.309

GnomAD4 genome

AF:

0.254

AC:

38608

AN:

152076

Hom.:

6299

Cov.:

AF XY:

0.262

AC XY:

19467

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.0635

Gnomad4 AMR

AF:

0.289

Gnomad4 ASJ

AF:

0.215

Gnomad4 EAS

AF:

0.378

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.437

Gnomad4 NFE

AF:

0.315

Gnomad4 OTH

AF:

0.277

Alfa

AF:

0.294

Hom.:

9069

Bravo

AF:

0.231

Asia WGS

AF:

0.390

AC:

1354

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Apr 04, 2023	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 29, 2016	- -

Ehlers-Danlos syndrome, kyphoscoliotic type 1

Benign:4

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Oct 25, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Jul 30, 2020	- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

not provided

Benign:1

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

-0.41

CADD

Benign

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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