chr15-73944779-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005576.4. 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
	LOXL1	NM_005576.4	MANE Select	c.1212-1638T>C		intron	N/A	NP_005567.2	Q08397

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.1212-1638T>C		intron	N/A	ENSP00000261921.7	Q08397
	LOXL1	ENST00000856631.1		c.1211+1817T>C		intron	N/A	ENSP00000526690.1
	LOXL1	ENST00000566011.5	TSL:5	n.*100-1638T>C		intron	N/A	ENSP00000457827.1	H3BUV8

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

African (AFR) AF: 0.536 AC: 22216 AN: 41484

American (AMR) AF: 0.629 AC: 9624 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.691 AC: 2397 AN: 3468

East Asian (EAS) AF: 0.424 AC: 2187 AN: 5154

South Asian (SAS) AF: 0.709 AC: 3413 AN: 4816

European-Finnish (FIN) AF: 0.755 AC: 7982 AN: 10566

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.768 AC: 52247 AN: 67988

Other (OTH) AF: 0.656 AC: 1382 AN: 2106

Alfa AF: 0.733 Hom.: 26534

Bravo AF: 0.659

Asia WGS AF: 0.534 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	8.9
DANN	Benign	0.78
PhyloP100		-0.53
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: rs1530169; hg19: chr15-74237120;