rs4243042

Positions:

• chr15-73949283-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):​c.1603-176A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 152,038 control chromosomes in the GnomAD database, including 12,009 homozygotes. 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: 𝑓 0.37 (12009 hom., cov: 32)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

Genes affected

LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1603-176A>T		intron_variant		ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.556-176A>T		intron_variant			XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1603-176A>T		intron_variant		1	NM_005576.4	ENSP00000261921	P1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56623 AN: 151920 Hom.: 12010 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.0890

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.372 AC: 56628 AN: 152038 Hom.: 12009 Cov.: 32 AF XY: 0.370 AC XY: 27495 AN XY: 74302

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.0892

Gnomad4 SAS AF: 0.317

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.377

Alfa AF: 0.431 Hom.: 1859

Bravo AF: 0.362

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.31
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs4243042; hg19: chr15-74241624;