dbSNP rs17524355: LOXL4:p.Ala569Ala (chr10-98253681-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

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

The NM_032211.7(LOXL4):c.1707G>A(p.Ala569Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,614,028 control chromosomes in the GnomAD database, including 30,891 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 0.18 ( 2647 hom., cov: 33)

Exomes 𝑓: 0.19 ( 28244 hom. )

Consequence

LOXL4
NM_032211.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.74

Variant links:

Genes affected

LOXL4 (HGNC:17171): (lysyl oxidase like 4) 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]

LOXL4 links:

ENSG00000230928 (HGNC:):

ENSG00000230928 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=-0.58).

BP7

Synonymous conserved (PhyloP=-3.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.201 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL4	NM_032211.7 link	c.1707G>A	p.Ala569Ala	synonymous_variant	Exon 11 of 15	ENST00000260702.4	NP_115587.6	Q96JB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL4	ENST00000260702.4 link	c.1707G>A	p.Ala569Ala	synonymous_variant	Exon 11 of 15	1	NM_032211.7	ENSP00000260702.3		Q96JB6
ENSG00000230928	ENST00000433374.1 link	n.180+1479C>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27454

AN:

152060

Hom.:

2649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.327

Gnomad AMR

AF:

0.147

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.0975

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.167

GnomAD3 exomes

AF:

0.169

AC:

42386

AN:

251428

Hom.:

4146

AF XY:

0.168

AC XY:

22801

AN XY:

135896

show subpopulations

Gnomad AFR exome

AF:

0.159

Gnomad AMR exome

AF:

0.116

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.0431

Gnomad SAS exome

AF:

0.0988

Gnomad FIN exome

AF:

0.267

Gnomad NFE exome

AF:

0.203

Gnomad OTH exome

AF:

0.179

GnomAD4 exome

AF:

0.191

AC:

278865

AN:

1461850

Hom.:

28244

Cov.:

AF XY:

0.189

AC XY:

137308

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.118

Gnomad4 ASJ exome

AF:

0.201

Gnomad4 EAS exome

AF:

0.0386

Gnomad4 SAS exome

AF:

0.0976

Gnomad4 FIN exome

AF:

0.264

Gnomad4 NFE exome

AF:

0.204

Gnomad4 OTH exome

AF:

0.186

GnomAD4 genome

AF:

0.180

AC:

27463

AN:

152178

Hom.:

2647

Cov.:

AF XY:

0.181

AC XY:

13439

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.156

Gnomad4 AMR

AF:

0.147

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.0338

Gnomad4 SAS

AF:

0.0965

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.171

Alfa

AF:

0.195

Hom.:

3914

Bravo

AF:

0.172

Asia WGS

AF:

0.100

AC:

348

AN:

3478

EpiCase

AF:

0.206

EpiControl

AF:

0.199

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

0.64

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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