rs1983864

chr10-98257696-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032211.7(LOXL4):c.1214A>C(p.Asp405Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.348 in 1,613,840 control chromosomes in the GnomAD database, including 103,485 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.30 (8234 hom., cov: 33)
  • Exomes 𝑓: 0.35 (95251 hom.)
• Consequence: LOXL4 NM_032211.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.02

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.586215E-4).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOXL4	NM_032211.7	c.1214A>C	p.Asp405Ala	missense_variant	8/15	ENST00000260702.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOXL4	ENST00000260702.4	c.1214A>C	p.Asp405Ala	missense_variant	8/15	1	NM_032211.7	P1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45473 AN: 152016 Hom.: 8228 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.324

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.445

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.308

GnomAD3 exomes AF: 0.387 AC: 97135 AN: 251288 Hom.: 20933 AF XY: 0.386 AC XY: 52367 AN XY: 135822

Gnomad AFR exome AF: 0.0963

Gnomad AMR exome AF: 0.585

Gnomad ASJ exome AF: 0.318

Gnomad EAS exome AF: 0.569

Gnomad SAS exome AF: 0.437

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.340

Gnomad OTH exome AF: 0.369

GnomAD4 exome AF: 0.353 AC: 515596 AN: 1461706 Hom.: 95251 Cov.: 44 AF XY: 0.355 AC XY: 257977 AN XY: 727176

Gnomad4 AFR exome AF: 0.0892

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.527

Gnomad4 SAS exome AF: 0.441

Gnomad4 FIN exome AF: 0.345

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.353

GnomAD4 genome AF: 0.299 AC: 45484 AN: 152134 Hom.: 8234 Cov.: 33 AF XY: 0.305 AC XY: 22699 AN XY: 74356

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.324

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.446

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.305

Alfa AF: 0.339 Hom.: 22374

Bravo AF: 0.297

TwinsUK AF: 0.331 AC: 1229

ALSPAC AF: 0.348 AC: 1343

ESP6500AA AF: 0.105 AC: 462

ESP6500EA AF: 0.327 AC: 2808

ExAC AF: 0.373 AC: 45329

Asia WGS AF: 0.478 AC: 1663 AN: 3478

EpiCase AF: 0.338

EpiControl AF: 0.335

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.23
Cadd	Pathogenic	28
Dann	Uncertain	1.0
DEOGEN2	Benign	0.27	T
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.74
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	1.0	D
MetaRNN	Benign	0.00096	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Uncertain	2.9	M
MutationTaster	Benign	9.0e-8	P
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.40
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.15	T
Polyphen		1.0	D
Vest4		0.33
MPC		0.60
ClinPred		0.044	T
GERP RS		5.5
Varity_R		0.96
gMVP		0.93

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

Other links and lift over

dbSNP: rs1983864; hg19: chr10-100017453; COSMIC: COSV53255033; COSMIC: COSV53255033;