15-73952003-C-T

Variant names:

• chr15-73952003-C-T
• rs3522
• NM_005576.4:c.*166C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):​c.*166C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 450,848 control chromosomes in the GnomAD database, including 50,114 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 0.48 (18068 hom., cov: 33)
  • Exomes 𝑓: 0.46 (32046 hom.)
• Consequence: LOXL1 NM_005576.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.830
• Publications: 29 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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	NM_005576.4	MANE Select	c.*166C>T		3_prime_UTR	Exon 7 of 7	NP_005567.2	Q08397

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.*166C>T		3_prime_UTR	Exon 7 of 7	ENSP00000261921.7	Q08397
	LOXL1	ENST00000856631.1		c.*166C>T		3_prime_UTR	Exon 6 of 6	ENSP00000526690.1
	LOXL1	ENST00000562548.1	TSL:2	n.976C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73258 AN: 152008 Hom.: 18034 Cov.: 33

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.584

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.458 AC: 136812 AN: 298722 Hom.: 32046 Cov.: 5 AF XY: 0.458 AC XY: 70451 AN XY: 153896

African (AFR) AF: 0.582 AC: 4715 AN: 8106

American (AMR) AF: 0.481 AC: 3902 AN: 8110

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 4223 AN: 9668

East Asian (EAS) AF: 0.645 AC: 15007 AN: 23274

South Asian (SAS) AF: 0.574 AC: 7028 AN: 12236

European-Finnish (FIN) AF: 0.437 AC: 10371 AN: 23720

Middle Eastern (MID) AF: 0.417 AC: 596 AN: 1430

European-Non Finnish (NFE) AF: 0.426 AC: 82645 AN: 194086

Other (OTH) AF: 0.460 AC: 8325 AN: 18092

GnomAD4 genome AF: 0.482 AC: 73357 AN: 152126 Hom.: 18068 Cov.: 33 AF XY: 0.486 AC XY: 36148 AN XY: 74386

African (AFR) AF: 0.574 AC: 23821 AN: 41526

American (AMR) AF: 0.476 AC: 7274 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1478 AN: 3468

East Asian (EAS) AF: 0.601 AC: 3108 AN: 5168

South Asian (SAS) AF: 0.583 AC: 2811 AN: 4824

European-Finnish (FIN) AF: 0.452 AC: 4785 AN: 10580

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.421 AC: 28589 AN: 67952

Other (OTH) AF: 0.482 AC: 1018 AN: 2114

Alfa AF: 0.438 Hom.: 27415

Bravo AF: 0.487

Asia WGS AF: 0.604 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.90
PhyloP100		-0.83
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: rs3522; hg19: chr15-74244344; COSMIC: COSV56096173; COSMIC: COSV56096173;