chr15-73952003-C-T

Position:

• chr15-73952003-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.*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

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=-0.72).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.*166C>T		3_prime_UTR_variant	7/7	ENST00000261921.8
LOXL1	XM_017022179.2	c.*166C>T		3_prime_UTR_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.*166C>T		3_prime_UTR_variant	7/7	1	NM_005576.4	P1
LOXL1	ENST00000562548.1	n.976C>T		non_coding_transcript_exon_variant	3/3	2
LOXL1	ENST00000567675.1	n.327C>T		non_coding_transcript_exon_variant	3/3	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

Gnomad4 AFR exome AF: 0.582

Gnomad4 AMR exome AF: 0.481

Gnomad4 ASJ exome AF: 0.437

Gnomad4 EAS exome AF: 0.645

Gnomad4 SAS exome AF: 0.574

Gnomad4 FIN exome AF: 0.437

Gnomad4 NFE exome AF: 0.426

Gnomad4 OTH exome AF: 0.460

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

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.476

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.601

Gnomad4 SAS AF: 0.583

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.482

Alfa AF: 0.431 Hom.: 19154

Bravo AF: 0.487

Asia WGS AF: 0.604 AC: 2102 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	2.4
DANN	Benign	0.90

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: rs3522; hg19: chr15-74244344; COSMIC: COSV56096173; COSMIC: COSV56096173;