rs893818

Variant names:

• chr15-73936854-G-A
• rs893818
• NM_005576.4:c.1103-6000G>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.1103-6000G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,212 control chromosomes in the GnomAD database, including 7,073 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 0.29 (7073 hom., cov: 34)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.555
• Publications: 19 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1103-6000G>A		intron_variant	Intron 1 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_011521555.3	c.1103-5021G>A		intron_variant	Intron 1 of 2		XP_011519857.1
LOXL1	XM_047432498.1	c.1103-5021G>A		intron_variant	Intron 1 of 2		XP_047288454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1103-6000G>A		intron_variant	Intron 1 of 6	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000566011.5	n.1103-5021G>A		intron_variant	Intron 1 of 7	5		ENSP00000457827.1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44597 AN: 152094 Hom.: 7069 Cov.: 34

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.303

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

GnomAD4 genome AF: 0.293 AC: 44626 AN: 152212 Hom.: 7073 Cov.: 34 AF XY: 0.296 AC XY: 22043 AN XY: 74410

African (AFR) AF: 0.193 AC: 8004 AN: 41524

American (AMR) AF: 0.327 AC: 5004 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2827 AN: 5164

South Asian (SAS) AF: 0.332 AC: 1601 AN: 4828

European-Finnish (FIN) AF: 0.313 AC: 3317 AN: 10600

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 22060 AN: 68008

Other (OTH) AF: 0.303 AC: 640 AN: 2114

Alfa AF: 0.320 Hom.: 13052

Bravo AF: 0.290

Asia WGS AF: 0.375 AC: 1307 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	10
DANN	Benign	0.71
PhyloP100		-0.56
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: rs893818; hg19: chr15-74229195;