dbSNP rs6985160: LOXL2:c.-83-147A>G (chr8-23368581-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002318.3(LOXL2):c.-83-147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 579,314 control chromosomes in the GnomAD database, including 140,497 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 0.73 ( 41003 hom., cov: 33)

Exomes 𝑓: 0.68 ( 99494 hom. )

Consequence

LOXL2
NM_002318.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.813

Publications

4 publications found

Variant links:

Genes affected

LOXL2 (HGNC:6666): (lysyl oxidase like 2) This gene encodes a member of the lysyl oxidase gene family. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyses the first step in the formation of crosslinks in collagens and elastin. 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. [provided by RefSeq, Jul 2008]

LOXL2 links:

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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=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL2	NM_002318.3 link	c.-83-147A>G		intron_variant	Intron 1 of 13	ENST00000389131.8	NP_002309.1	Q9Y4K0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL2	ENST00000389131.8 link	c.-83-147A>G		intron_variant	Intron 1 of 13	1	NM_002318.3	ENSP00000373783.3		Q9Y4K0

Frequencies

GnomAD3 genomes

AF:

0.727

AC:

110621

AN:

152086

Hom.:

40939

Cov.:

show subpopulations

Gnomad AFR

AF:

0.843

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.762

Gnomad ASJ

AF:

0.637

Gnomad EAS

AF:

0.847

Gnomad SAS

AF:

0.574

Gnomad FIN

AF:

0.720

Gnomad MID

AF:

0.481

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.717

GnomAD4 exome

AF:

0.677

AC:

289013

AN:

427110

Hom.:

99494

AF XY:

0.669

AC XY:

150350

AN XY:

224730

show subpopulations

African (AFR)

AF:

0.837

AC:

10135

AN:

12104

American (AMR)

AF:

0.794

AC:

14483

AN:

18234

Ashkenazi Jewish (ASJ)

AF:

0.617

AC:

8172

AN:

13242

East Asian (EAS)

AF:

0.874

AC:

25558

AN:

29258

South Asian (SAS)

AF:

0.570

AC:

25208

AN:

44226

European-Finnish (FIN)

AF:

0.723

AC:

19639

AN:

27176

Middle Eastern (MID)

AF:

0.613

AC:

1146

AN:

1870

European-Non Finnish (NFE)

AF:

0.655

AC:

167893

AN:

256220

Other (OTH)

AF:

0.677

AC:

16779

AN:

24780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

4341

8683

13024

17366

21707

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.728

AC:

110744

AN:

152204

Hom.:

41003

Cov.:

AF XY:

0.730

AC XY:

54281

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.843

AC:

35000

AN:

41532

American (AMR)

AF:

0.762

AC:

11654

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.637

AC:

2213

AN:

3472

East Asian (EAS)

AF:

0.847

AC:

4375

AN:

5166

South Asian (SAS)

AF:

0.574

AC:

2768

AN:

4824

European-Finnish (FIN)

AF:

0.720

AC:

7627

AN:

10596

Middle Eastern (MID)

AF:

0.486

AC:

143

AN:

294

European-Non Finnish (NFE)

AF:

0.659

AC:

44794

AN:

67998

Other (OTH)

AF:

0.719

AC:

1519

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1531

3062

4593

6124

7655

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<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:

0.683

Hom.:

7257

Bravo

AF:

0.742

Asia WGS

AF:

0.685

AC:

2382

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

0.88

(source)

DANN

Benign

0.33

PhyloP100

-0.81

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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