rs74026313

Variant names:

• chr15-73947272-G-A
• rs74026313
• NM_005576.4:c.1506+49G>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.1506+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,554,318 control chromosomes in the GnomAD database, including 5,387 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 0.11 (1493 hom., cov: 34)
  • Exomes 𝑓: 0.067 (3894 hom.)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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.1506+49G>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.1506+49G>A		intron	N/A	ENSP00000261921.7	Q08397
	LOXL1	ENST00000856631.1		c.1368+49G>A		intron	N/A	ENSP00000526690.1
	LOXL1	ENST00000562548.1	TSL:2	n.57G>A		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16881 AN: 152164 Hom.: 1490 Cov.: 34

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0587

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0622

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0690

Gnomad OTH AF: 0.0937

GnomAD2 exomes AF: 0.0692 AC: 15092 AN: 218170 AF XY: 0.0663

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.0410

Gnomad ASJ exome AF: 0.0760

Gnomad EAS exome AF: 0.00171

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0686

Gnomad OTH exome AF: 0.0636

GnomAD4 exome AF: 0.0666 AC: 93359 AN: 1402036 Hom.: 3894 Cov.: 29 AF XY: 0.0657 AC XY: 45280 AN XY: 689304

African (AFR) AF: 0.244 AC: 7840 AN: 32084

American (AMR) AF: 0.0429 AC: 1715 AN: 39932

Ashkenazi Jewish (ASJ) AF: 0.0743 AC: 1726 AN: 23218

East Asian (EAS) AF: 0.000830 AC: 32 AN: 38572

South Asian (SAS) AF: 0.0584 AC: 4622 AN: 79176

European-Finnish (FIN) AF: 0.0364 AC: 1855 AN: 50914

Middle Eastern (MID) AF: 0.0901 AC: 468 AN: 5196

European-Non Finnish (NFE) AF: 0.0660 AC: 71009 AN: 1075298

Other (OTH) AF: 0.0710 AC: 4092 AN: 57646

GnomAD4 genome AF: 0.111 AC: 16899 AN: 152282 Hom.: 1493 Cov.: 34 AF XY: 0.108 AC XY: 8028 AN XY: 74472

African (AFR) AF: 0.244 AC: 10144 AN: 41534

American (AMR) AF: 0.0585 AC: 896 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5180

South Asian (SAS) AF: 0.0621 AC: 300 AN: 4832

European-Finnish (FIN) AF: 0.0343 AC: 364 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0690 AC: 4693 AN: 68020

Other (OTH) AF: 0.0951 AC: 201 AN: 2114

Alfa AF: 0.0943 Hom.: 511

Bravo AF: 0.119

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	11
DANN	Benign	0.69
PhyloP100		1.1
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: rs74026313; hg19: chr15-74239613; COSMIC: COSV56096843; COSMIC: COSV56096843;