15-73944779-T-C

Variant names:

• chr15-73944779-T-C
• rs1530169
• NM_005576.4:c.1212-1638T>C

Variant summary

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

The NM_005576.4(LOXL1):​c.1212-1638T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,078 control chromosomes in the GnomAD database, including 35,403 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 0.67 (35403 hom., cov: 32)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.525

Genes affected

LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. 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. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1212-1638T>C		intron_variant	Intron 2 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.165-1638T>C		intron_variant	Intron 2 of 6		XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1212-1638T>C		intron_variant	Intron 2 of 6	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000566011.5	n.*100-1638T>C		intron_variant	Intron 3 of 7	5		ENSP00000457827.1

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102283 AN: 151960 Hom.: 35398 Cov.: 32

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.716

Gnomad AMR AF: 0.630

Gnomad ASJ AF: 0.691

Gnomad EAS AF: 0.425

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.755

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.768

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.673 AC: 102323 AN: 152078 Hom.: 35403 Cov.: 32 AF XY: 0.670 AC XY: 49795 AN XY: 74310

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.629

Gnomad4 ASJ AF: 0.691

Gnomad4 EAS AF: 0.424

Gnomad4 SAS AF: 0.709

Gnomad4 FIN AF: 0.755

Gnomad4 NFE AF: 0.768

Gnomad4 OTH AF: 0.656

Alfa AF: 0.736 Hom.: 23382

Bravo AF: 0.659

Asia WGS AF: 0.534 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.9
DANN	Benign	0.78

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: rs1530169; hg19: chr15-74237120;