1-11934753-C-T

Variant names:

• chr1-11934753-C-T
• rs1252431057
• NM_000302.4:c.-27C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000302.4(PLOD1):​c.-27C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000584 in 1,370,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000058 (0 hom.)
• Consequence: PLOD1 NM_000302.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.296
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, PanelApp Australia, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLOD1	NM_000302.4	c.-27C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	ENST00000196061.5	NP_000293.2
PLOD1	NM_000302.4	c.-27C>T		5_prime_UTR_variant	Exon 1 of 19	ENST00000196061.5	NP_000293.2
PLOD1	NM_001316320.2	c.-27C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 20		NP_001303249.1
PLOD1	NM_001316320.2	c.-27C>T		5_prime_UTR_variant	Exon 1 of 20		NP_001303249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD1	ENST00000196061.5	c.-27C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 19	1	NM_000302.4	ENSP00000196061.4
PLOD1	ENST00000196061.5	c.-27C>T		5_prime_UTR_variant	Exon 1 of 19	1	NM_000302.4	ENSP00000196061.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000171 AC: 2 AN: 117228 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000138

Gnomad NFE exome AF: 0.0000227

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000584 AC: 8 AN: 1370466 Hom.: 0 Cov.: 31 AF XY: 0.00000296 AC XY: 2 AN XY: 676224

African (AFR) AF: 0.00 AC: 0 AN: 28580

American (AMR) AF: 0.00 AC: 0 AN: 34552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24552

East Asian (EAS) AF: 0.00 AC: 0 AN: 33448

South Asian (SAS) AF: 0.00 AC: 0 AN: 77246

European-Finnish (FIN) AF: 0.0000268 AC: 1 AN: 37284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4344

European-Non Finnish (NFE) AF: 0.00000466 AC: 5 AN: 1073300

Other (OTH) AF: 0.0000350 AC: 2 AN: 57160

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Benign	0.90
PhyloP100		-0.30
PromoterAI		-0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs1252431057; hg19: chr1-11994810;