rs2304721

Variant names:

• chr15-73948013-C-A
• rs2304721
• NM_005576.4:c.1602+111C>A

Your query was ambiguous. Multiple possible variants found:

• chr15-73948013-C-A
• chr15-73948013-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):​c.1602+111C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 719,662 control chromosomes in the GnomAD database, including 1,844 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 0.054 (344 hom., cov: 33)
  • Exomes 𝑓: 0.057 (1500 hom.)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.60
• Publications: 11 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 (EAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1602+111C>A		intron_variant	Intron 5 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.555+111C>A		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.1602+111C>A		intron_variant	Intron 5 of 6	1	NM_005576.4	ENSP00000261921.7

Frequencies

GnomAD3 genomes AF: 0.0545 AC: 8292 AN: 152158 Hom.: 349 Cov.: 33

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0893

Gnomad ASJ AF: 0.0957

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0387

Gnomad OTH AF: 0.0707

GnomAD4 exome AF: 0.0573 AC: 32538 AN: 567386 Hom.: 1500 AF XY: 0.0586 AC XY: 17243 AN XY: 294426

African (AFR) AF: 0.0343 AC: 476 AN: 13870

American (AMR) AF: 0.0746 AC: 1349 AN: 18078

Ashkenazi Jewish (ASJ) AF: 0.0908 AC: 1224 AN: 13486

East Asian (EAS) AF: 0.211 AC: 6135 AN: 29130

South Asian (SAS) AF: 0.0996 AC: 4230 AN: 42466

European-Finnish (FIN) AF: 0.0517 AC: 2258 AN: 43646

Middle Eastern (MID) AF: 0.0718 AC: 263 AN: 3664

European-Non Finnish (NFE) AF: 0.0393 AC: 14709 AN: 374700

Other (OTH) AF: 0.0668 AC: 1894 AN: 28346

GnomAD4 genome AF: 0.0544 AC: 8290 AN: 152276 Hom.: 344 Cov.: 33 AF XY: 0.0580 AC XY: 4321 AN XY: 74448

African (AFR) AF: 0.0368 AC: 1528 AN: 41564

American (AMR) AF: 0.0892 AC: 1365 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0957 AC: 332 AN: 3470

East Asian (EAS) AF: 0.237 AC: 1223 AN: 5162

South Asian (SAS) AF: 0.105 AC: 508 AN: 4830

European-Finnish (FIN) AF: 0.0498 AC: 528 AN: 10608

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2636 AN: 68018

Other (OTH) AF: 0.0695 AC: 147 AN: 2116

Alfa AF: 0.0461 Hom.: 1060

Bravo AF: 0.0562

Asia WGS AF: 0.196 AC: 680 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	0.011
DANN	Benign	0.78
PhyloP100		-4.6
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: rs2304721; hg19: chr15-74240354; COSMIC: COSV56095388;