rs12437465

Variant names:

• chr15-73950905-T-C
• rs12437465
• NM_005576.4:c.1719-926T>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.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
• Publications: 8 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=-0.85).
• 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 rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1719-926T>C		intron_variant	Intron 6 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.672-926T>C		intron_variant	Intron 6 of 6		XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1719-926T>C		intron_variant	Intron 6 of 6	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000562548.1	n.804-926T>C		intron_variant	Intron 2 of 2	2
LOXL1	ENST00000566011.5	n.*607-926T>C		intron_variant	Intron 7 of 7	5		ENSP00000457827.1
LOXL1	ENST00000567675.1	n.155-926T>C		intron_variant	Intron 2 of 2	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

African (AFR) AF: 0.303 AC: 12570 AN: 41438

American (AMR) AF: 0.414 AC: 6324 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.393 AC: 1365 AN: 3472

East Asian (EAS) AF: 0.454 AC: 2349 AN: 5178

South Asian (SAS) AF: 0.465 AC: 2242 AN: 4818

European-Finnish (FIN) AF: 0.413 AC: 4365 AN: 10572

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.424 AC: 28829 AN: 67968

Other (OTH) AF: 0.399 AC: 843 AN: 2114

Alfa AF: 0.407 Hom.: 27226

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
PhyloP100		-2.0
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: rs12437465; hg19: chr15-74243246;