chr15-73951937-C-T

Variant names:

• chr15-73951937-C-T
• rs8818
• NM_005576.4:c.*100C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005576.4(LOXL1):​c.*100C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000994 in 1,005,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 9.9e-7 (0 hom.)
• Consequence: LOXL1 NM_005576.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.*100C>T		3_prime_UTR_variant	Exon 7 of 7	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.*100C>T		3_prime_UTR_variant	Exon 7 of 7		XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.*100C>T		3_prime_UTR_variant	Exon 7 of 7	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000562548.1	n.910C>T		non_coding_transcript_exon_variant	Exon 3 of 3	2
LOXL1	ENST00000567675.1	n.261C>T		non_coding_transcript_exon_variant	Exon 3 of 3	3
LOXL1	ENST00000566011.5	n.*713C>T		downstream_gene_variant		5		ENSP00000457827.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 9.94e-7 AC: 1 AN: 1005774 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 490150

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21326

American (AMR) AF: 0.00 AC: 0 AN: 12330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14434

East Asian (EAS) AF: 0.00 AC: 0 AN: 27948

South Asian (SAS) AF: 0.0000270 AC: 1 AN: 37044

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33128

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2776

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 815656

Other (OTH) AF: 0.00 AC: 0 AN: 41132

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.95
PhyloP100		0.51

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: rs8818; hg19: chr15-74244278;