15-73927743-G-T

Variant names:

• chr15-73927743-G-T
• rs41435250
• NM_005576.4:c.960G>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005576.4(LOXL1):​c.960G>T​(p.Ala320Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,455,754 control chromosomes in the GnomAD database, including 1,803 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 0.041 (296 hom., cov: 33)
  • Exomes 𝑓: 0.028 (1507 hom.)
• Consequence: LOXL1 NM_005576.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 19 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]

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP7: Synonymous conserved (PhyloP=0.172 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 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.960G>T	p.Ala320Ala	synonymous	Exon 1 of 7	NP_005567.2
	LOXL1-AS1	NR_040066.1		n.44C>A		non_coding_transcript_exon	Exon 1 of 4
	LOXL1-AS1	NR_040067.1		n.44C>A		non_coding_transcript_exon	Exon 1 of 4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.960G>T	p.Ala320Ala	synonymous	Exon 1 of 7	ENSP00000261921.7
	LOXL1	ENST00000566011.5	TSL:5	n.960G>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000457827.1
	LOXL1-AS1	ENST00000567257.5	TSL:2	n.44C>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6176 AN: 151998 Hom.: 299 Cov.: 33

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.0403

Gnomad MID AF: 0.0545

Gnomad NFE AF: 0.0166

Gnomad OTH AF: 0.0550

GnomAD2 exomes AF: 0.0614 AC: 4121 AN: 67162 AF XY: 0.0626

Gnomad AFR exome AF: 0.0271

Gnomad AMR exome AF: 0.0663

Gnomad ASJ exome AF: 0.0928

Gnomad EAS exome AF: 0.263

Gnomad FIN exome AF: 0.0399

Gnomad NFE exome AF: 0.0172

Gnomad OTH exome AF: 0.0546

GnomAD4 exome AF: 0.0282 AC: 36753 AN: 1303648 Hom.: 1507 Cov.: 33 AF XY: 0.0300 AC XY: 19240 AN XY: 642048

African (AFR) AF: 0.0281 AC: 739 AN: 26270

American (AMR) AF: 0.0662 AC: 1545 AN: 23324

Ashkenazi Jewish (ASJ) AF: 0.0894 AC: 2012 AN: 22496

East Asian (EAS) AF: 0.214 AC: 6021 AN: 28174

South Asian (SAS) AF: 0.0938 AC: 6590 AN: 70256

European-Finnish (FIN) AF: 0.0400 AC: 1301 AN: 32490

Middle Eastern (MID) AF: 0.0575 AC: 236 AN: 4104

European-Non Finnish (NFE) AF: 0.0150 AC: 15625 AN: 1042554

Other (OTH) AF: 0.0497 AC: 2684 AN: 53980

GnomAD4 genome AF: 0.0406 AC: 6172 AN: 152106 Hom.: 296 Cov.: 33 AF XY: 0.0446 AC XY: 3320 AN XY: 74364

African (AFR) AF: 0.0304 AC: 1265 AN: 41550

American (AMR) AF: 0.0771 AC: 1179 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1235 AN: 5144

South Asian (SAS) AF: 0.101 AC: 487 AN: 4830

European-Finnish (FIN) AF: 0.0403 AC: 426 AN: 10560

Middle Eastern (MID) AF: 0.0517 AC: 15 AN: 290

European-Non Finnish (NFE) AF: 0.0166 AC: 1128 AN: 67946

Other (OTH) AF: 0.0544 AC: 115 AN: 2114

Alfa AF: 0.0262 Hom.: 14

Bravo AF: 0.0419

Asia WGS AF: 0.199 AC: 682 AN: 3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.17
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: rs41435250; hg19: chr15-74220084; COSMIC: COSV56094000; COSMIC: COSV56094000;