Variant rs74026313 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005576.4(LOXL1):c.1506+49G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0709 in 1,554,318 control chromosomes in the GnomAD database, including 5,387 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 0.11 ( 1493 hom., cov: 34)

Exomes 𝑓: 0.067 ( 3894 hom. )

Consequence

LOXL1
NM_005576.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.11

Variant links:

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]

LOXL1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4 linkuse as main transcript	c.1506+49G>A		intron_variant		ENST00000261921.8
LOXL1	XM_017022179.2 linkuse as main transcript	c.459+49G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
LOXL1	ENST00000261921.8 linkuse as main transcript	c.1506+49G>A	intron_variant		1	NM_005576.4	P1
LOXL1	ENST00000562548.1 linkuse as main transcript	n.57G>A	non_coding_transcript_exon_variant	1/3	2
LOXL1	ENST00000566011.5 linkuse as main transcript	c.*394+49G>A	intron_variant, NMD_transcript_variant		5
LOXL1	ENST00000566530.1 linkuse as main transcript	n.344+49G>A	intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16881

AN:

152164

Hom.:

1490

Cov.:

show subpopulations

Gnomad AFR

AF:

0.245

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.0587

Gnomad ASJ

AF:

0.0723

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0622

Gnomad FIN

AF:

0.0343

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0690

Gnomad OTH

AF:

0.0937

GnomAD3 exomes

AF:

0.0692

AC:

15092

AN:

218170

Hom.:

870

AF XY:

0.0663

AC XY:

7732

AN XY:

116630

show subpopulations

Gnomad AFR exome

AF:

0.252

Gnomad AMR exome

AF:

0.0410

Gnomad ASJ exome

AF:

0.0760

Gnomad EAS exome

AF:

0.00171

Gnomad SAS exome

AF:

0.0624

Gnomad FIN exome

AF:

0.0341

Gnomad NFE exome

AF:

0.0686

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0666

AC:

93359

AN:

1402036

Hom.:

3894

Cov.:

AF XY:

0.0657

AC XY:

45280

AN XY:

689304

show subpopulations

Gnomad4 AFR exome

AF:

0.244

Gnomad4 AMR exome

AF:

0.0429

Gnomad4 ASJ exome

AF:

0.0743

Gnomad4 EAS exome

AF:

0.000830

Gnomad4 SAS exome

AF:

0.0584

Gnomad4 FIN exome

AF:

0.0364

Gnomad4 NFE exome

AF:

0.0660

Gnomad4 OTH exome

AF:

0.0710

GnomAD4 genome

AF:

0.111

AC:

16899

AN:

152282

Hom.:

1493

Cov.:

AF XY:

0.108

AC XY:

8028

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.0585

Gnomad4 ASJ

AF:

0.0723

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0621

Gnomad4 FIN

AF:

0.0343

Gnomad4 NFE

AF:

0.0690

Gnomad4 OTH

AF:

0.0951

Alfa

AF:

0.102

Hom.:

235

Bravo

AF:

0.119

Asia WGS

AF:

0.0550

AC:

191

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over