rs4886776

Variant names:

• chr15-73932655-G-A
• rs4886776
• NM_005576.4:c.1102+4770G>A

Your query was ambiguous. Multiple possible variants found:

• chr15-73932655-G-A
• chr15-73932655-G-C

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+4770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,076 control chromosomes in the GnomAD database, including 6,799 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 0.28 (6799 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100
• Publications: 16 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005576.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	NM_005576.4	MANE Select	c.1102+4770G>A		intron	N/A	NP_005567.2	Q08397

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.1102+4770G>A		intron	N/A	ENSP00000261921.7	Q08397
	LOXL1	ENST00000856631.1		c.1102+4770G>A		intron	N/A	ENSP00000526690.1
	LOXL1	ENST00000566011.5	TSL:5	n.1102+4770G>A		intron	N/A	ENSP00000457827.1	H3BUV8

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43285 AN: 151958 Hom.: 6797 Cov.: 33

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.324

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.285 AC: 43296 AN: 152076 Hom.: 6799 Cov.: 33 AF XY: 0.287 AC XY: 21358 AN XY: 74336

African (AFR) AF: 0.164 AC: 6807 AN: 41468

American (AMR) AF: 0.326 AC: 4991 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3472

East Asian (EAS) AF: 0.548 AC: 2830 AN: 5168

South Asian (SAS) AF: 0.332 AC: 1600 AN: 4820

European-Finnish (FIN) AF: 0.309 AC: 3268 AN: 10562

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.324 AC: 21998 AN: 67982

Other (OTH) AF: 0.299 AC: 629 AN: 2104

Alfa AF: 0.313 Hom.: 30543

Bravo AF: 0.281

Asia WGS AF: 0.364 AC: 1270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.53
PhyloP100		-0.10
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: rs4886776; hg19: chr15-74224996;