ENST00000485046.5:n.119+172G>A

Variant names:

• chr1-11934495-G-A
• rs79541392
• ENST00000485046.5:n.119+172G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000485046.5(PLOD1):​n.119+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 152,158 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.015 (62 hom., cov: 32)
• Consequence: PLOD1 ENST00000485046.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, kyphoscoliotic type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-11934495-G-A is Benign according to our data. Variant chr1-11934495-G-A is described in ClinVar as Benign. ClinVar VariationId is 1271435.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0506 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000485046.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLOD1	NM_000302.4	MANE Select	c.-285G>A		upstream_gene	N/A	NP_000293.2
	PLOD1	NM_001316320.2		c.-285G>A		upstream_gene	N/A	NP_001303249.1	Q02809-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLOD1	ENST00000485046.5	TSL:5	n.119+172G>A		intron	N/A
	PLOD1	ENST00000196061.5	TSL:1 MANE Select	c.-285G>A		upstream_gene	N/A	ENSP00000196061.4	Q02809-1
	PLOD1	ENST00000854019.1		c.-285G>A		upstream_gene	N/A	ENSP00000524078.1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2317 AN: 152040 Hom.: 62 Cov.: 32

Gnomad AFR AF: 0.0525

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0101

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

GnomAD4 genome AF: 0.0153 AC: 2321 AN: 152158 Hom.: 62 Cov.: 32 AF XY: 0.0143 AC XY: 1062 AN XY: 74406

African (AFR) AF: 0.0525 AC: 2176 AN: 41484

American (AMR) AF: 0.00701 AC: 107 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 67986

Other (OTH) AF: 0.00996 AC: 21 AN: 2108

Alfa AF: 0.0174 Hom.: 28

Bravo AF: 0.0179

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.81
DANN	Benign	0.79
PhyloP100		-1.4
PromoterAI		0.020	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79541392; hg19: chr1-11994552;