10-98253133-A-G

Position:

• chr10-98253133-A-G

Variant summary

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

The NM_032211.7(LOXL4):​c.1835+420T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,090 control chromosomes in the GnomAD database, including 26,878 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 0.59 (26878 hom., cov: 33)
• Consequence: LOXL4 NM_032211.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOXL4	NM_032211.7	c.1835+420T>C		intron_variant		ENST00000260702.4	NP_115587.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOXL4	ENST00000260702.4	c.1835+420T>C		intron_variant		1	NM_032211.7	ENSP00000260702	P1
	ENST00000433374.1	n.180+931A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89458 AN: 151974 Hom.: 26867 Cov.: 33

Gnomad AFR AF: 0.453

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.597

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.698

Gnomad MID AF: 0.631

Gnomad NFE AF: 0.641

Gnomad OTH AF: 0.598

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.589 AC: 89507 AN: 152090 Hom.: 26878 Cov.: 33 AF XY: 0.592 AC XY: 44023 AN XY: 74330

Gnomad4 AFR AF: 0.453

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.597

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.665

Gnomad4 FIN AF: 0.698

Gnomad4 NFE AF: 0.641

Gnomad4 OTH AF: 0.599

Alfa AF: 0.630 Hom.: 16206

Bravo AF: 0.575

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs737657; hg19: chr10-100012890;