Variant rs1983864 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
LOXL4	NM_032211.7 linkuse as main transcript	c.1214A>C	p.Asp405Ala	missense_variant	8/15	ENST00000260702.4	NP_115587.6	Q96JB6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL4	ENST00000260702.4 linkuse as main transcript	c.1214A>C	p.Asp405Ala	missense_variant	8/15	1	NM_032211.7	ENSP00000260702.3		Q96JB6

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45473

AN:

152016

Hom.:

8228

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.355

AC XY:

257977

AN XY:

727176

show subpopulations

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.:

AF XY:

0.305

AC XY:

22699

AN XY:

74356

show subpopulations

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

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.74

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

1.0

MetaRNN

Benign

0.00096

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.9

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-6.7

REVEL

Uncertain

0.40

Sift

Pathogenic

0.0

Sift4G

Benign

0.15

Polyphen

1.0

Vest4

0.33

MPC

0.60

ClinPred

0.044

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

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