rs1247487702

Variant names:

• chr15-73926985-C-T
• rs1247487702
• NM_005576.4:c.202C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-73926985-C-T
• chr15-73926985-C-A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005576.4(LOXL1):​c.202C>T​(p.Arg68Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000467 in 1,499,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R68H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000045 (0 hom.)
• Consequence: LOXL1 NM_005576.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.375
• 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]

LOXL1-AS1 (HGNC:44169): (LOXL1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13756743).

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.202C>T	p.Arg68Cys	missense	Exon 1 of 7	NP_005567.2	Q08397
	LOXL1-AS1	NR_040066.1		n.133+669G>A		intron	N/A
	LOXL1-AS1	NR_040067.1		n.133+669G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOXL1	ENST00000261921.8	TSL:1 MANE Select	c.202C>T	p.Arg68Cys	missense	Exon 1 of 7	ENSP00000261921.7	Q08397
	LOXL1	ENST00000856631.1		c.202C>T	p.Arg68Cys	missense	Exon 1 of 6	ENSP00000526690.1
	LOXL1	ENST00000566011.5	TSL:5	n.202C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000457827.1	H3BUV8

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000445 AC: 6 AN: 1347116 Hom.: 0 Cov.: 30 AF XY: 0.00000151 AC XY: 1 AN XY: 662480

African (AFR) AF: 0.00 AC: 0 AN: 27732

American (AMR) AF: 0.00 AC: 0 AN: 30726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23540

East Asian (EAS) AF: 0.00 AC: 0 AN: 30480

South Asian (SAS) AF: 0.00 AC: 0 AN: 74632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5328

European-Non Finnish (NFE) AF: 0.00000570 AC: 6 AN: 1051794

Other (OTH) AF: 0.00 AC: 0 AN: 55306

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152088 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.071	N
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.38
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.045
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.10	T
Polyphen		0.82	P
Vest4		0.14
MutPred		0.19		Gain of helix (P = 0.0349)
MVP		0.30
ClinPred		0.34	T
GERP RS		-4.9
Varity_R		0.16
gMVP		0.28
Mutation Taster		=85/15	polymorphism

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: rs1247487702; hg19: chr15-74219326;