rs2273286

chr1-11952352-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000302.4(PLOD1):c.467-271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0646 in 152,188 control chromosomes in the GnomAD database, including 387 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.065 (387 hom., cov: 32)
• Consequence: PLOD1 NM_000302.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.199

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 1-11952352-A-G is Benign according to our data. Variant chr1-11952352-A-G is described in ClinVar as [Benign]. Clinvar id is 669464.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLOD1	NM_000302.4	c.467-271A>G		intron_variant		ENST00000196061.5
PLOD1	NM_001316320.2	c.608-271A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLOD1	ENST00000196061.5	c.467-271A>G		intron_variant		1	NM_000302.4	P1

Frequencies

GnomAD3 genomes AF: 0.0646 AC: 9830 AN: 152070 Hom.: 386 Cov.: 32

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0322

Gnomad ASJ AF: 0.0262

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0723

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.0594

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

GnomAD4 genome AF: 0.0646 AC: 9832 AN: 152188 Hom.: 387 Cov.: 32 AF XY: 0.0654 AC XY: 4869 AN XY: 74418

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.0320

Gnomad4 ASJ AF: 0.0262

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0723

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.0593

Alfa AF: 0.0568 Hom.: 78

Bravo AF: 0.0604

Asia WGS AF: 0.141 AC: 490 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.7
Dann	Benign	0.44

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: rs2273286; hg19: chr1-12012409;