rs8041642

Variant names:

• chr15-73932765-G-A
• rs8041642
• NM_005576.4:c.1102+4880G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.88).
• 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 rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1102+4880G>A		intron_variant	Intron 1 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_011521555.3	c.1102+4880G>A		intron_variant	Intron 1 of 2		XP_011519857.1
LOXL1	XM_047432498.1	c.1102+4880G>A		intron_variant	Intron 1 of 2		XP_047288454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1102+4880G>A		intron_variant	Intron 1 of 6	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000566011.5	n.1102+4880G>A		intron_variant	Intron 1 of 7	5		ENSP00000457827.1

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

African (AFR) AF: 0.323 AC: 13421 AN: 41506

American (AMR) AF: 0.150 AC: 2302 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 601 AN: 3470

East Asian (EAS) AF: 0.123 AC: 640 AN: 5184

South Asian (SAS) AF: 0.246 AC: 1188 AN: 4828

European-Finnish (FIN) AF: 0.165 AC: 1750 AN: 10602

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11086 AN: 68004

Other (OTH) AF: 0.194 AC: 411 AN: 2114

Alfa AF: 0.185 Hom.: 681

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
PhyloP100		0.14
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: rs8041642; hg19: chr15-74225106;