15-73929861-T-C

Variant summary

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

The NM_005576.4(LOXL1):c.1102+1976T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,122 control chromosomes in the GnomAD database, including 29,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

• Frequency: Genomes: 𝑓 0.60 (29038 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: risk factor no assertion criteria provided O:1
• Conservation: PhyloP100: 0.193

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.1102+1976T>C		intron_variant		ENST00000261921.8
LOXL1	XM_011521555.3	c.1102+1976T>C		intron_variant
LOXL1	XM_047432498.1	c.1102+1976T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.1102+1976T>C		intron_variant		1	NM_005576.4	P1
LOXL1	ENST00000566011.5	c.1102+1976T>C		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91788 AN: 152004 Hom.: 29003 Cov.: 33

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.523

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.514

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.604 AC: 91877 AN: 152122 Hom.: 29038 Cov.: 33 AF XY: 0.607 AC XY: 45167 AN XY: 74354

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.523

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.514

Gnomad4 NFE AF: 0.503

Gnomad4 OTH AF: 0.594

Alfa AF: 0.526 Hom.: 29274

Bravo AF: 0.614

Asia WGS AF: 0.784 AC: 2729 AN: 3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Exfoliation syndrome, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

May 01, 2009

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	13
Dann	Benign	0.83

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: rs2165241; hg19: chr15-74222202;