1-11965296-T-C

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.1471-184T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,858 control chromosomes in the GnomAD database, including 27,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.58 (27365 hom., cov: 30)
• Consequence: PLOD1 NM_000302.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.03

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=-0.94).
• BP6: Variant 1-11965296-T-C is Benign according to our data. Variant chr1-11965296-T-C is described in ClinVar as [Benign]. Clinvar id is 1263662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PLOD1	NM_000302.4	c.1471-184T>C		intron_variant		ENST00000196061.5
PLOD1	NM_001316320.2	c.1612-184T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PLOD1	ENST00000196061.5	c.1471-184T>C		intron_variant		1	NM_000302.4	P1
PLOD1	ENST00000470133.1	n.85-184T>C		intron_variant, non_coding_transcript_variant		3
PLOD1	ENST00000491536.5	n.99-184T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87623 AN: 151740 Hom.: 27325 Cov.: 30

Gnomad AFR AF: 0.808

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.682

Gnomad SAS AF: 0.658

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.540

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

GnomAD4 genome AF: 0.578 AC: 87727 AN: 151858 Hom.: 27365 Cov.: 30 AF XY: 0.580 AC XY: 43049 AN XY: 74212

Gnomad4 AFR AF: 0.808

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.657

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.541

Alfa AF: 0.479 Hom.: 22084

Bravo AF: 0.575

Asia WGS AF: 0.695 AC: 2415 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 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.56
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2273291; hg19: chr1-12025353;