15-73934799-A-T

Variant names:

• chr15-73934799-A-T
• rs12594472
• NM_005576.4:c.1102+6914A>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.1102+6914A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,218 control chromosomes in the GnomAD database, including 1,008 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 0.084 (1008 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1102+6914A>T		intron_variant	Intron 1 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_011521555.3	c.1102+6914A>T		intron_variant	Intron 1 of 2		XP_011519857.1
LOXL1	XM_047432498.1	c.1102+6914A>T		intron_variant	Intron 1 of 2		XP_047288454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1102+6914A>T		intron_variant	Intron 1 of 6	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000566011.5	n.1102+6914A>T		intron_variant	Intron 1 of 7	5		ENSP00000457827.1

Frequencies

GnomAD3 genomes AF: 0.0845 AC: 12847 AN: 152100 Hom.: 1010 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0880

Gnomad ASJ AF: 0.0919

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0404

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0156

Gnomad OTH AF: 0.0823

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

GnomAD4 genome AF: 0.0844 AC: 12852 AN: 152218 Hom.: 1008 Cov.: 33 AF XY: 0.0869 AC XY: 6466 AN XY: 74428

African (AFR) AF: 0.187 AC: 7772 AN: 41504

American (AMR) AF: 0.0880 AC: 1347 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0919 AC: 319 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1243 AN: 5174

South Asian (SAS) AF: 0.102 AC: 491 AN: 4818

European-Finnish (FIN) AF: 0.0404 AC: 429 AN: 10608

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1060 AN: 68018

Other (OTH) AF: 0.0814 AC: 172 AN: 2112

Alfa AF: 0.0526 Hom.: 67

Bravo AF: 0.0915

Asia WGS AF: 0.203 AC: 706 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.70
PhyloP100		-1.6
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: rs12594472; hg19: chr15-74227140;