rs41435250

chr15-73927743-G-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005576.4(LOXL1):c.960G>T(p.Ala320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,455,754 control chromosomes in the GnomAD database, including 1,803 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 0.041 (296 hom., cov: 33)
  • Exomes 𝑓: 0.028 (1507 hom.)
• Consequence: LOXL1 NM_005576.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172

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]

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.172 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.960G>T	p.Ala320=	synonymous_variant	1/7	ENST00000261921.8
LOXL1-AS1	NR_040069.1	n.184+322C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.960G>T	p.Ala320=	synonymous_variant	1/7	1	NM_005576.4	P1
LOXL1-AS1	ENST00000685373.1	n.198+34C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6176 AN: 151998 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0550

GnomAD3 exomes AF: 0.0614 AC: 4121 AN: 67162 Hom.: 244 AF XY: 0.0626 AC XY: 2450 AN XY: 39148

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.0928

Gnomad EAS exome AF: 0.263

Gnomad SAS exome AF: 0.0972

Gnomad FIN exome AF: 0.0399

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0546

GnomAD4 exome AF: 0.0282 AC: 36753 AN: 1303648 Hom.: 1507 Cov.: 33 AF XY: 0.0300 AC XY: 19240 AN XY: 642048

Gnomad4 AFR exome AF: 0.0281

Gnomad4 AMR exome AF: 0.0662

Gnomad4 ASJ exome AF: 0.0894

Gnomad4 EAS exome AF: 0.214

Gnomad4 SAS exome AF: 0.0938

Gnomad4 FIN exome AF: 0.0400

Gnomad4 NFE exome AF: 0.0150

Gnomad4 OTH exome AF: 0.0497

GnomAD4 genome AF: 0.0406 AC: 6172 AN: 152106 Hom.: 296 Cov.: 33 AF XY: 0.0446 AC XY: 3320 AN XY: 74364

Gnomad4 AFR AF: 0.0304

Gnomad4 AMR AF: 0.0771

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0403

Gnomad4 NFE AF: 0.0166

Gnomad4 OTH AF: 0.0544

Alfa AF: 0.0262 Hom.: 14

Bravo AF: 0.0419

Asia WGS AF: 0.199 AC: 682 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
Cadd	Benign	12
Dann	Benign	0.64

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: rs41435250; hg19: chr15-74220084; COSMIC: COSV56094000; COSMIC: COSV56094000;