chr15-73934424-G-C

Variant names:

• chr15-73934424-G-C
• rs4337252
• NM_005576.4:c.1102+6539G>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+6539G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,956 control chromosomes in the GnomAD database, including 20,728 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 0.52 (20728 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 24 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	NM_005576.4	MANE Select	c.1102+6539G>C		intron	N/A	NP_005567.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.1102+6539G>C		intron	N/A	ENSP00000261921.7
	LOXL1	ENST00000856631.1		c.1102+6539G>C		intron	N/A	ENSP00000526690.1
	LOXL1	ENST00000566011.5	TSL:5	n.1102+6539G>C		intron	N/A	ENSP00000457827.1

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78675 AN: 151838 Hom.: 20701 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.518 AC: 78762 AN: 151956 Hom.: 20728 Cov.: 33 AF XY: 0.519 AC XY: 38562 AN XY: 74246

African (AFR) AF: 0.577 AC: 23911 AN: 41420

American (AMR) AF: 0.485 AC: 7405 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.430 AC: 1492 AN: 3472

East Asian (EAS) AF: 0.670 AC: 3448 AN: 5144

South Asian (SAS) AF: 0.578 AC: 2784 AN: 4814

European-Finnish (FIN) AF: 0.473 AC: 4993 AN: 10552

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33126 AN: 67976

Other (OTH) AF: 0.512 AC: 1077 AN: 2104

Alfa AF: 0.494 Hom.: 2332

Bravo AF: 0.521

Asia WGS AF: 0.575 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.69
PhyloP100		-1.2
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: rs4337252; hg19: chr15-74226765;