chr15-73951556-G-A

Variant names:

• chr15-73951556-G-A
• rs12441138
• NM_005576.4:c.1719-275G>A

Variant summary

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

The NM_005576.4(LOXL1):​c.1719-275G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0565 in 152,178 control chromosomes in the GnomAD database, including 401 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 0.057 (401 hom., cov: 32)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• 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=-0.48).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.18 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1719-275G>A		intron_variant	Intron 6 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.672-275G>A		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.1719-275G>A		intron_variant	Intron 6 of 6	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000562548.1	n.804-275G>A		intron_variant	Intron 2 of 2	2
LOXL1	ENST00000566011.5	n.*607-275G>A		intron_variant	Intron 7 of 7	5		ENSP00000457827.1
LOXL1	ENST00000567675.1	n.155-275G>A		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.0564 AC: 8578 AN: 152060 Hom.: 398 Cov.: 32

Gnomad AFR AF: 0.107

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0356

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.0927

Gnomad FIN AF: 0.0204

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0651

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

GnomAD4 genome AF: 0.0565 AC: 8599 AN: 152178 Hom.: 401 Cov.: 32 AF XY: 0.0566 AC XY: 4209 AN XY: 74396

African (AFR) AF: 0.107 AC: 4456 AN: 41510

American (AMR) AF: 0.0355 AC: 544 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0922 AC: 320 AN: 3472

East Asian (EAS) AF: 0.190 AC: 981 AN: 5168

South Asian (SAS) AF: 0.0915 AC: 442 AN: 4830

European-Finnish (FIN) AF: 0.0204 AC: 216 AN: 10582

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0218 AC: 1479 AN: 67992

Other (OTH) AF: 0.0682 AC: 144 AN: 2112

Alfa AF: 0.0483 Hom.: 206

Bravo AF: 0.0604

Asia WGS AF: 0.172 AC: 597 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12441138; hg19: chr15-74243897;