rs750460

Positions:

• chr15-73949165-G-A
• chr15-73949165-G-C
• chr15-73949165-G-T

Variant summary

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

The NM_005576.4(LOXL1):​c.1603-294G>A 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 152,090 control chromosomes in the GnomAD database, including 11,975 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 (11975 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0440

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]

LOXL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.1603-294G>A		intron_variant		ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.556-294G>A		intron_variant			XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1603-294G>A		intron_variant		1	NM_005576.4	ENSP00000261921.7

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56517 AN: 151972 Hom.: 11976 Cov.: 33

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.0891

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.579

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.380

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

GnomAD4 genome AF: 0.372 AC: 56522 AN: 152090 Hom.: 11975 Cov.: 33 AF XY: 0.369 AC XY: 27444 AN XY: 74336

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.412

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.0893

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.479

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.376

Alfa AF: 0.454 Hom.: 26023

Bravo AF: 0.361

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.63

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: rs750460; hg19: chr15-74241506;