Variant chr15-73927659-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2

The NM_005576.4(LOXL1):c.876C>T(p.Asp292=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0343 in 1,487,556 control chromosomes in the GnomAD database, including 1,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.025 ( 58 hom., cov: 33)

Exomes 𝑓: 0.035 ( 961 hom. )

Consequence

LOXL1
NM_005576.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.807

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 15-73927659-C-T is Benign according to our data. Variant chr15-73927659-C-T is described in ClinVar as [Benign]. Clinvar id is 3038417.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-0.807 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0248 (3771/152144) while in subpopulation NFE AF= 0.0359 (2440/67958). AF 95% confidence interval is 0.0347. There are 58 homozygotes in gnomad4. There are 1861 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL1	NM_005576.4 linkuse as main transcript	c.876C>T	p.Asp292=	synonymous_variant	1/7	ENST00000261921.8
LOXL1-AS1	NR_040069.1 linkuse as main transcript	n.184+406G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL1	ENST00000261921.8 linkuse as main transcript	c.876C>T	p.Asp292=	synonymous_variant	1/7	1	NM_005576.4	P1
LOXL1-AS1	ENST00000685373.1 linkuse as main transcript	n.198+118G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0248

AC:

3773

AN:

152036

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00662

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0225

Gnomad ASJ

AF:

0.0109

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.0498

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0359

Gnomad OTH

AF:

0.0292

GnomAD3 exomes

AF:

0.0247

AC:

2073

AN:

83938

Hom.:

AF XY:

0.0244

AC XY:

1166

AN XY:

47884

show subpopulations

Gnomad AFR exome

AF:

0.00783

Gnomad AMR exome

AF:

0.0150

Gnomad ASJ exome

AF:

0.00874

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.0562

Gnomad NFE exome

AF:

0.0385

Gnomad OTH exome

AF:

0.0266

GnomAD4 exome

AF:

0.0354

AC:

47259

AN:

1335412

Hom.:

961

Cov.:

AF XY:

0.0343

AC XY:

22576

AN XY:

658576

show subpopulations

Gnomad4 AFR exome

AF:

0.00549

Gnomad4 AMR exome

AF:

0.0169

Gnomad4 ASJ exome

AF:

0.00891

Gnomad4 EAS exome

AF:

0.0000341

Gnomad4 SAS exome

AF:

0.0114

Gnomad4 FIN exome

AF:

0.0492

Gnomad4 NFE exome

AF:

0.0400

Gnomad4 OTH exome

AF:

0.0274

GnomAD4 genome

AF:

0.0248

AC:

3771

AN:

152144

Hom.:

Cov.:

AF XY:

0.0250

AC XY:

1861

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00660

Gnomad4 AMR

AF:

0.0223

Gnomad4 ASJ

AF:

0.0109

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.0120

Gnomad4 FIN

AF:

0.0498

Gnomad4 NFE

AF:

0.0359

Gnomad4 OTH

AF:

0.0289

Alfa

AF:

0.0268

Hom.:

Bravo

AF:

0.0229

Asia WGS

AF:

0.00609

AC:

AN:

3462

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

LOXL1-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 25, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

3.5

DANN

Benign

0.90

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over