dbSNP rs16958477: LOXL1:n.-659A>C (chr15-73926125-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000566011.5(LOXL1):n.-659A>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,436 control chromosomes in the GnomAD database, including 9,467 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 0.33 ( 9442 hom., cov: 32)

Exomes 𝑓: 0.33 ( 25 hom. )

Consequence

LOXL1
ENST00000566011.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0720

Publications

26 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOXL1-AS1	NR_040066.1 link	n.134-620T>G	intron_variant	Intron 1 of 3
LOXL1-AS1	NR_040067.1 link	n.134-620T>G	intron_variant	Intron 1 of 3
LOXL1-AS1	NR_040068.1 link	n.184+1940T>G	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein
LOXL1	ENST00000566011.5 link	n.-659A>C	non_coding_transcript_exon_variant	Exon 1 of 8	5	ENSP00000457827.1
LOXL1	ENST00000566011.5 link	n.-659A>C	5_prime_UTR_variant	Exon 1 of 8	5	ENSP00000457827.1
LOXL1-AS1	ENST00000562130.5 link	n.103+115T>G	intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.328

AC:

49782

AN:

151968

Hom.:

9442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.421

Gnomad AMR

AF:

0.382

Gnomad ASJ

AF:

0.399

Gnomad EAS

AF:

0.0864

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.405

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.426

Gnomad OTH

AF:

0.342

GnomAD4 exome

AF:

0.331

AC:

116

AN:

350

Hom.:

Cov.:

AF XY:

0.327

AC XY:

AN XY:

266

show subpopulations

African (AFR)

AF:

0.188

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.346

AC:

AN:

Middle Eastern (MID)

AF:

1.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.342

AC:

AN:

266

Other (OTH)

AF:

0.600

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.327

AC:

49786

AN:

152086

Hom.:

9442

Cov.:

AF XY:

0.324

AC XY:

24049

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.160

AC:

6625

AN:

41506

American (AMR)

AF:

0.382

AC:

5838

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.399

AC:

1385

AN:

3470

East Asian (EAS)

AF:

0.0866

AC:

449

AN:

5184

South Asian (SAS)

AF:

0.219

AC:

1056

AN:

4820

European-Finnish (FIN)

AF:

0.405

AC:

4291

AN:

10584

Middle Eastern (MID)

AF:

0.483

AC:

142

AN:

294

European-Non Finnish (NFE)

AF:

0.426

AC:

28904

AN:

67928

Other (OTH)

AF:

0.338

AC:

713

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1608

3215

4823

6430

8038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.368

Hom.:

9573

Bravo

AF:

0.320

Asia WGS

AF:

0.144

AC:

502

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.2

(source)

DANN

Benign

0.54

PhyloP100

-0.072

PromoterAI

-0.021

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over