Variant rs41435250 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_005576.4(LOXL1):c.960G>T(p.Ala320=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0295 in 1,455,754 control chromosomes in the GnomAD database, including 1,803 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 0.041 ( 296 hom., cov: 33)

Exomes 𝑓: 0.028 ( 1507 hom. )

Consequence

LOXL1
NM_005576.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.172

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:

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

LOXL1-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP7

Synonymous conserved (PhyloP=0.172 with no splicing effect.

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/exons	MANE	Protein	UniProt
LOXL1	NM_005576.4 linkuse as main transcript	c.960G>T	p.Ala320=	synonymous_variant	1/7	ENST00000261921.8	NP_005567.2
LOXL1-AS1	NR_040069.1 linkuse as main transcript	n.184+322C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8 linkuse as main transcript	c.960G>T	p.Ala320=	synonymous_variant	1/7	1	NM_005576.4	ENSP00000261921	P1
LOXL1-AS1	ENST00000685373.1 linkuse as main transcript	n.198+34C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0406

AC:

6176

AN:

151998

Hom.:

299

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0771

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.102

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.0545

Gnomad NFE

AF:

0.0166

Gnomad OTH

AF:

0.0550

GnomAD3 exomes

AF:

0.0614

AC:

4121

AN:

67162

Hom.:

244

AF XY:

0.0626

AC XY:

2450

AN XY:

39148

show subpopulations

Gnomad AFR exome

AF:

0.0271

Gnomad AMR exome

AF:

0.0663

Gnomad ASJ exome

AF:

0.0928

Gnomad EAS exome

AF:

0.263

Gnomad SAS exome

AF:

0.0972

Gnomad FIN exome

AF:

0.0399

Gnomad NFE exome

AF:

0.0172

Gnomad OTH exome

AF:

0.0546

GnomAD4 exome

AF:

0.0282

AC:

36753

AN:

1303648

Hom.:

1507

Cov.:

AF XY:

0.0300

AC XY:

19240

AN XY:

642048

show subpopulations

Gnomad4 AFR exome

AF:

0.0281

Gnomad4 AMR exome

AF:

0.0662

Gnomad4 ASJ exome

AF:

0.0894

Gnomad4 EAS exome

AF:

0.214

Gnomad4 SAS exome

AF:

0.0938

Gnomad4 FIN exome

AF:

0.0400

Gnomad4 NFE exome

AF:

0.0150

Gnomad4 OTH exome

AF:

0.0497

GnomAD4 genome

AF:

0.0406

AC:

6172

AN:

152106

Hom.:

296

Cov.:

AF XY:

0.0446

AC XY:

3320

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.0304

Gnomad4 AMR

AF:

0.0771

Gnomad4 ASJ

AF:

0.0922

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.101

Gnomad4 FIN

AF:

0.0403

Gnomad4 NFE

AF:

0.0166

Gnomad4 OTH

AF:

0.0544

Alfa

AF:

0.0262

Hom.:

Bravo

AF:

0.0419

Asia WGS

AF:

0.199

AC:

682

AN:

3436

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.64

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