NM_032211.7:c.1835+420T>C

Variant names:

• chr10-98253133-A-G
• rs737657
• NM_032211.7:c.1835+420T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL4	NM_032211.7	MANE Select	c.1835+420T>C		intron	N/A	NP_115587.6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL4	ENST00000260702.4	TSL:1 MANE Select	c.1835+420T>C		intron	N/A	ENSP00000260702.3	Q96JB6
	ENSG00000230928	ENST00000433374.1	TSL:1	n.180+931A>G		intron	N/A
	LOXL4	ENST00000905881.1		c.1862+420T>C		intron	N/A	ENSP00000575940.1

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

African (AFR) AF: 0.453 AC: 18781 AN: 41472

American (AMR) AF: 0.637 AC: 9741 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.597 AC: 2068 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2662 AN: 5162

South Asian (SAS) AF: 0.665 AC: 3214 AN: 4830

European-Finnish (FIN) AF: 0.698 AC: 7381 AN: 10578

Middle Eastern (MID) AF: 0.637 AC: 186 AN: 292

European-Non Finnish (NFE) AF: 0.641 AC: 43561 AN: 67978

Other (OTH) AF: 0.599 AC: 1267 AN: 2114

Alfa AF: 0.627 Hom.: 21945

Bravo AF: 0.575

Asia WGS AF: 0.607 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	9.5
DANN	Benign	0.63
PhyloP100		0.31
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs737657; hg19: chr10-100012890;