rs4886782

Variant names:

• chr15-73936469-G-A
• rs4886782
• NM_005576.4:c.1103-6385G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):​c.1103-6385G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.268 in 152,198 control chromosomes in the GnomAD database, including 6,754 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 0.27 (6754 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.440
• Publications: 25 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	NM_005576.4	MANE Select	c.1103-6385G>A		intron	N/A	NP_005567.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.1103-6385G>A		intron	N/A	ENSP00000261921.7
	LOXL1	ENST00000566011.5	TSL:5	n.1103-5406G>A		intron	N/A	ENSP00000457827.1

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40845 AN: 152080 Hom.: 6755 Cov.: 33

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.343

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.363

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.268 AC: 40847 AN: 152198 Hom.: 6754 Cov.: 33 AF XY: 0.266 AC XY: 19827 AN XY: 74410

African (AFR) AF: 0.0896 AC: 3721 AN: 41542

American (AMR) AF: 0.330 AC: 5052 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 1190 AN: 3468

East Asian (EAS) AF: 0.0822 AC: 426 AN: 5184

South Asian (SAS) AF: 0.181 AC: 875 AN: 4826

European-Finnish (FIN) AF: 0.363 AC: 3838 AN: 10582

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24683 AN: 67984

Other (OTH) AF: 0.274 AC: 579 AN: 2114

Alfa AF: 0.335 Hom.: 15368

Bravo AF: 0.260

Asia WGS AF: 0.124 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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: rs4886782; hg19: chr15-74228810;