rs2304719

Variant names:

• chr15-73943159-C-T
• rs2304719
• NM_005576.4:c.1211+197C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):​c.1211+197C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,058 control chromosomes in the GnomAD database, including 7,076 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 0.30 (7076 hom., cov: 32)
• Consequence: LOXL1 NM_005576.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.59
• Publications: 14 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=-1.02).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.1211+197C>T		intron_variant	Intron 2 of 6	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.164+197C>T		intron_variant	Intron 2 of 6		XP_016877668.1
LOXL1	XM_047432498.1	c.*296C>T		downstream_gene_variant			XP_047288454.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.1211+197C>T		intron_variant	Intron 2 of 6	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000566011.5	n.*99+197C>T		intron_variant	Intron 3 of 7	5		ENSP00000457827.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45375 AN: 151940 Hom.: 7073 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.279

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.332

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.299 AC: 45407 AN: 152058 Hom.: 7076 Cov.: 32 AF XY: 0.298 AC XY: 22158 AN XY: 74324

African (AFR) AF: 0.341 AC: 14145 AN: 41462

American (AMR) AF: 0.215 AC: 3279 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 836 AN: 3468

East Asian (EAS) AF: 0.331 AC: 1712 AN: 5166

South Asian (SAS) AF: 0.387 AC: 1867 AN: 4824

European-Finnish (FIN) AF: 0.276 AC: 2920 AN: 10576

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19762 AN: 67982

Other (OTH) AF: 0.274 AC: 578 AN: 2110

Alfa AF: 0.290 Hom.: 23560

Bravo AF: 0.295

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.072
DANN	Benign	0.77
PhyloP100		-3.6
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: rs2304719; hg19: chr15-74235500;