chr10-98253681-C-T

Variant names:

• chr10-98253681-C-T
• rs17524355
• NM_032211.7:c.1707G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.74
• Publications: 14 publications found

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 Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000230928 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032211.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL4	NM_032211.7	MANE Select	c.1707G>A	p.Ala569Ala	synonymous	Exon 11 of 15	NP_115587.6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL4	ENST00000260702.4	TSL:1 MANE Select	c.1707G>A	p.Ala569Ala	synonymous	Exon 11 of 15	ENSP00000260702.3
	ENSG00000230928	ENST00000433374.1	TSL:1	n.180+1479C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27454 AN: 152060 Hom.: 2649 Cov.: 33

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

GnomAD2 exomes AF: 0.169 AC: 42386 AN: 251428 AF XY: 0.168

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 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.: 37 AF XY: 0.189 AC XY: 137308 AN XY: 727220

African (AFR) AF: 0.156 AC: 5222 AN: 33478

American (AMR) AF: 0.118 AC: 5289 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 5245 AN: 26136

East Asian (EAS) AF: 0.0386 AC: 1532 AN: 39700

South Asian (SAS) AF: 0.0976 AC: 8417 AN: 86258

European-Finnish (FIN) AF: 0.264 AC: 14089 AN: 53418

Middle Eastern (MID) AF: 0.156 AC: 901 AN: 5768

European-Non Finnish (NFE) AF: 0.204 AC: 226927 AN: 1111978

Other (OTH) AF: 0.186 AC: 11243 AN: 60394

GnomAD4 genome AF: 0.180 AC: 27463 AN: 152178 Hom.: 2647 Cov.: 33 AF XY: 0.181 AC XY: 13439 AN XY: 74386

African (AFR) AF: 0.156 AC: 6458 AN: 41516

American (AMR) AF: 0.147 AC: 2247 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 707 AN: 3472

East Asian (EAS) AF: 0.0338 AC: 175 AN: 5172

South Asian (SAS) AF: 0.0965 AC: 466 AN: 4828

European-Finnish (FIN) AF: 0.268 AC: 2833 AN: 10574

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13860 AN: 68006

Other (OTH) AF: 0.171 AC: 362 AN: 2114

Alfa AF: 0.193 Hom.: 4713

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.64
DANN	Benign	0.91
PhyloP100		-3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17524355; hg19: chr10-100013438; COSMIC: COSV53256411;