rs893817

Positions:

• chr15-73936724-G-A
• chr15-73936724-G-C

Variant summary

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

The NM_005576.4(LOXL1):​c.1103-6130G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.664 in 152,146 control chromosomes in the GnomAD database, including 33,801 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 0.66 (33801 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.1103-6130G>A		intron_variant		ENST00000261921.8
LOXL1	XM_011521555.3	c.1103-5151G>A		intron_variant
LOXL1	XM_047432498.1	c.1103-5151G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.1103-6130G>A		intron_variant		1	NM_005576.4	P1
LOXL1	ENST00000566011.5	c.1103-5151G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.664 AC: 100913 AN: 152028 Hom.: 33790 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.647

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.715

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.679

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.653

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.664 AC: 100967 AN: 152146 Hom.: 33801 Cov.: 33 AF XY: 0.663 AC XY: 49311 AN XY: 74364

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.715

Gnomad4 EAS AF: 0.451

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.679

Gnomad4 NFE AF: 0.653

Gnomad4 OTH AF: 0.652

Alfa AF: 0.652 Hom.: 50383

Bravo AF: 0.664

Asia WGS AF: 0.590 AC: 2048 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.48
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs893817; hg19: chr15-74229065;