rs8041642

Positions:

• chr15-73932765-G-A

Variant summary

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

The NM_005576.4(LOXL1):​c.1102+4880G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,218 control chromosomes in the GnomAD database, including 3,750 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 0.21 (3750 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.142

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.1102+4880G>A		intron_variant		ENST00000261921.8
LOXL1	XM_011521555.3	c.1102+4880G>A		intron_variant
LOXL1	XM_047432498.1	c.1102+4880G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.1102+4880G>A		intron_variant		1	NM_005576.4	P1
LOXL1	ENST00000566011.5	c.1102+4880G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31605 AN: 152100 Hom.: 3744 Cov.: 33

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.194

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31644 AN: 152218 Hom.: 3750 Cov.: 33 AF XY: 0.207 AC XY: 15413 AN XY: 74422

Gnomad4 AFR AF: 0.323

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.123

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.194

Alfa AF: 0.182 Hom.: 639

Bravo AF: 0.211

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.5
DANN	Benign	0.78

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: rs8041642; hg19: chr15-74225106;