rs3818157

Variant names:

• chr1-11967251-G-A
• rs3818157
• NM_000302.4:c.1755+160G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-11967251-G-A
• chr1-11967251-G-C
• chr1-11967251-G-T

Variant summary

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

The NM_000302.4(PLOD1):​c.1755+160G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 151,736 control chromosomes in the GnomAD database, including 20,013 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.51 (20013 hom., cov: 30)
• Consequence: PLOD1 NM_000302.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.704
• Publications: 15 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-11967251-G-A is Benign according to our data. Variant chr1-11967251-G-A is described in ClinVar as Benign. ClinVar VariationId is 1285712.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLOD1	NM_000302.4	c.1755+160G>A		intron_variant	Intron 16 of 18	ENST00000196061.5	NP_000293.2
PLOD1	NM_001316320.2	c.1896+160G>A		intron_variant	Intron 17 of 19		NP_001303249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD1	ENST00000196061.5	c.1755+160G>A		intron_variant	Intron 16 of 18	1	NM_000302.4	ENSP00000196061.4
PLOD1	ENST00000491536.5	n.383+160G>A		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76698 AN: 151618 Hom.: 20004 Cov.: 30

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.636

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.506 AC: 76752 AN: 151736 Hom.: 20013 Cov.: 30 AF XY: 0.510 AC XY: 37808 AN XY: 74090

African (AFR) AF: 0.576 AC: 23838 AN: 41390

American (AMR) AF: 0.435 AC: 6630 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3464

East Asian (EAS) AF: 0.636 AC: 3257 AN: 5124

South Asian (SAS) AF: 0.629 AC: 3020 AN: 4800

European-Finnish (FIN) AF: 0.566 AC: 5967 AN: 10550

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.465 AC: 31525 AN: 67860

Other (OTH) AF: 0.484 AC: 1024 AN: 2114

Alfa AF: 0.476 Hom.: 57510

Bravo AF: 0.494

Asia WGS AF: 0.639 AC: 2222 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 23, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3818157; hg19: chr1-12027308;