rs11553676

Positions:

• chr1-11964293-C-A
• chr1-11964293-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4 BP6_Moderate BP7

The NM_000302.4(PLOD1):​c.1321C>A​(p.Arg441Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 26)
• Consequence: PLOD1 NM_000302.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.747

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP6: Variant 1-11964293-C-A is Benign according to our data. Variant chr1-11964293-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 1140492.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.747 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLOD1	NM_000302.4	c.1321C>A	p.Arg441Arg	synonymous_variant	12/19	ENST00000196061.5	NP_000293.2
PLOD1	NM_001316320.2	c.1462C>A	p.Arg488Arg	synonymous_variant	13/20		NP_001303249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLOD1	ENST00000196061.5	c.1321C>A	p.Arg441Arg	synonymous_variant	12/19	1	NM_000302.4	ENSP00000196061.4

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 16

GnomAD4 genome Cov.: 26

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ehlers-Danlos syndrome, kyphoscoliotic type 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 14, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	12
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-12024350;