NM_005576.4:c.1102+1976T>C

Variant names:

• chr15-73929861-T-C
• rs2165241
• NM_005576.4:c.1102+1976T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 107 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 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.1102+1976T>C		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.1102+1976T>C		intron	N/A	ENSP00000261921.7
	LOXL1	ENST00000566011.5	TSL:5	n.1102+1976T>C		intron	N/A	ENSP00000457827.1

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

African (AFR) AF: 0.767 AC: 31854 AN: 41534

American (AMR) AF: 0.575 AC: 8786 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1814 AN: 3470

East Asian (EAS) AF: 0.911 AC: 4709 AN: 5170

South Asian (SAS) AF: 0.682 AC: 3292 AN: 4824

European-Finnish (FIN) AF: 0.514 AC: 5445 AN: 10590

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.503 AC: 34177 AN: 67934

Other (OTH) AF: 0.594 AC: 1254 AN: 2110

Alfa AF: 0.533 Hom.: 37955

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

May 01, 2009

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.19
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: rs2165241; hg19: chr15-74222202;