rs2304722

Variant names:

• chr15-73949408-T-C
• rs2304722
• NM_005576.4:c.1603-51T>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.1603-51T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,069,342 control chromosomes in the GnomAD database, including 20,465 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 0.18 (2668 hom., cov: 32)
  • Exomes 𝑓: 0.19 (17797 hom.)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1603-51T>C		intron_variant	Intron 5 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.556-51T>C		intron_variant	Intron 5 of 6		XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1603-51T>C		intron_variant	Intron 5 of 6	1	NM_005576.4	ENSP00000261921.7

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27464 AN: 152030 Hom.: 2666 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.348

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.199

GnomAD2 exomes AF: 0.202 AC: 50611 AN: 250046 AF XY: 0.204

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.246

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.344

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.179

Gnomad OTH exome AF: 0.212

GnomAD4 exome AF: 0.192 AC: 176219 AN: 917194 Hom.: 17797 Cov.: 13 AF XY: 0.193 AC XY: 92479 AN XY: 478418

African (AFR) AF: 0.148 AC: 3432 AN: 23222

American (AMR) AF: 0.249 AC: 10973 AN: 44004

Ashkenazi Jewish (ASJ) AF: 0.205 AC: 4661 AN: 22688

East Asian (EAS) AF: 0.361 AC: 13444 AN: 37286

South Asian (SAS) AF: 0.203 AC: 15280 AN: 75220

European-Finnish (FIN) AF: 0.183 AC: 9706 AN: 53136

Middle Eastern (MID) AF: 0.213 AC: 1005 AN: 4716

European-Non Finnish (NFE) AF: 0.179 AC: 109681 AN: 614456

Other (OTH) AF: 0.189 AC: 8037 AN: 42466

GnomAD4 genome AF: 0.181 AC: 27478 AN: 152148 Hom.: 2668 Cov.: 32 AF XY: 0.184 AC XY: 13699 AN XY: 74394

African (AFR) AF: 0.139 AC: 5785 AN: 41516

American (AMR) AF: 0.245 AC: 3743 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 709 AN: 3472

East Asian (EAS) AF: 0.348 AC: 1800 AN: 5170

South Asian (SAS) AF: 0.204 AC: 983 AN: 4810

European-Finnish (FIN) AF: 0.188 AC: 1998 AN: 10602

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11828 AN: 67992

Other (OTH) AF: 0.199 AC: 420 AN: 2110

Alfa AF: 0.183 Hom.: 1099

Bravo AF: 0.183

Asia WGS AF: 0.229 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.012
DANN	Benign	0.65
PhyloP100		-1.8
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: rs2304722; hg19: chr15-74241749; COSMIC: COSV56096444;