rs16958477

chr15-73926125-A-C

Variant summary

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

The NR_040069.1(LOXL1-AS1):n.184+1940T>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,436 control chromosomes in the GnomAD database, including 9,467 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 0.33 (9442 hom., cov: 32)
  • Exomes 𝑓: 0.33 (25 hom.)
• Consequence: LOXL1-AS1 NR_040069.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720

Genes affected

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

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1-AS1	NR_040069.1	n.184+1940T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1-AS1	ENST00000685373.1	n.198+1652T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49782 AN: 151968 Hom.: 9442 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.399

Gnomad EAS AF: 0.0864

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.342

GnomAD4 exome AF: 0.331 AC: 116 AN: 350 Hom.: 25 Cov.: 0 AF XY: 0.327 AC XY: 87 AN XY: 266

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.346

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.600

GnomAD4 genome AF: 0.327 AC: 49786 AN: 152086 Hom.: 9442 Cov.: 32 AF XY: 0.324 AC XY: 24049 AN XY: 74324

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.382

Gnomad4 ASJ AF: 0.399

Gnomad4 EAS AF: 0.0866

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.426

Gnomad4 OTH AF: 0.338

Alfa AF: 0.394 Hom.: 7474

Bravo AF: 0.320

Asia WGS AF: 0.144 AC: 502 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	2.2
Dann	Benign	0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16958477; hg19: chr15-74218466;