rs12437465

chr15-73950905-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):c.1719-926T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 152,042 control chromosomes in the GnomAD database, including 11,889 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 0.39 (11889 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4	c.1719-926T>C		intron_variant		ENST00000261921.8
LOXL1	XM_017022179.2	c.672-926T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8	c.1719-926T>C		intron_variant		1	NM_005576.4	P1
LOXL1	ENST00000566011.5	c.*607-926T>C		intron_variant, NMD_transcript_variant		5
LOXL1	ENST00000562548.1	n.804-926T>C		intron_variant, non_coding_transcript_variant		2
LOXL1	ENST00000567675.1	n.155-926T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59339 AN: 151926 Hom.: 11886 Cov.: 33

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.465

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.424

Gnomad OTH AF: 0.400

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

GnomAD4 genome AF: 0.390 AC: 59367 AN: 152042 Hom.: 11889 Cov.: 33 AF XY: 0.394 AC XY: 29294 AN XY: 74330

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.465

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.424

Gnomad4 OTH AF: 0.399

Alfa AF: 0.418 Hom.: 18439

Bravo AF: 0.383

Asia WGS AF: 0.417 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.37
Dann	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs12437465; hg19: chr15-74243246;