rs2304721

Positions:

• chr15-73948013-C-A
• chr15-73948013-C-T

Variant summary

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

The NM_005576.4(LOXL1):​c.1602+111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 719,662 control chromosomes in the GnomAD database, including 1,844 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 0.054 (344 hom., cov: 33)
  • Exomes 𝑓: 0.057 (1500 hom.)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.60

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 (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.1602+111C>A		intron_variant		ENST00000261921.8
LOXL1	XM_017022179.2	c.555+111C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.1602+111C>A		intron_variant		1	NM_005576.4	P1

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8292 AN: 152158 Hom.: 349 Cov.: 33

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0387

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.0573 AC: 32538 AN: 567386 Hom.: 1500 AF XY: 0.0586 AC XY: 17243 AN XY: 294426

Gnomad4 AFR exome AF: 0.0343

Gnomad4 AMR exome AF: 0.0746

Gnomad4 ASJ exome AF: 0.0908

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.0996

Gnomad4 FIN exome AF: 0.0517

Gnomad4 NFE exome AF: 0.0393

Gnomad4 OTH exome AF: 0.0668

GnomAD4 genome AF: 0.0544 AC: 8290 AN: 152276 Hom.: 344 Cov.: 33 AF XY: 0.0580 AC XY: 4321 AN XY: 74448

Gnomad4 AFR AF: 0.0368

Gnomad4 AMR AF: 0.0892

Gnomad4 ASJ AF: 0.0957

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0498

Gnomad4 NFE AF: 0.0388

Gnomad4 OTH AF: 0.0695

Alfa AF: 0.0439 Hom.: 381

Bravo AF: 0.0562

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	-0.88
CADD	Benign	0.011
DANN	Benign	0.78

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: rs2304721; hg19: chr15-74240354; COSMIC: COSV56095388;