15-73934424-G-C

Position:

• chr15-73934424-G-C

Variant summary

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

The NM_005576.4(LOXL1):​c.1102+6539G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,956 control chromosomes in the GnomAD database, including 20,728 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 0.52 (20728 hom., cov: 33)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1102+6539G>C		intron_variant		ENST00000261921.8	NP_005567.2
LOXL1	XM_011521555.3	c.1102+6539G>C		intron_variant			XP_011519857.1
LOXL1	XM_047432498.1	c.1102+6539G>C		intron_variant			XP_047288454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1102+6539G>C		intron_variant		1	NM_005576.4	ENSP00000261921	P1
LOXL1	ENST00000566011.5	c.1102+6539G>C		intron_variant, NMD_transcript_variant		5		ENSP00000457827

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78675 AN: 151838 Hom.: 20701 Cov.: 33

Gnomad AFR AF: 0.577

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.473

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.518 AC: 78762 AN: 151956 Hom.: 20728 Cov.: 33 AF XY: 0.519 AC XY: 38562 AN XY: 74246

Gnomad4 AFR AF: 0.577

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.670

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.473

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.512

Alfa AF: 0.494 Hom.: 2332

Bravo AF: 0.521

Asia WGS AF: 0.575 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.69

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: rs4337252; hg19: chr15-74226765;