rs7173049

Variant names:

• chr15-73952269-A-G
• rs7173049
• NM_005576.4:c.*432A>G

Your query was ambiguous. Multiple possible variants found:

• chr15-73952269-A-G
• chr15-73952269-A-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005576.4(LOXL1):​c.*432A>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 161,388 control chromosomes in the GnomAD database, including 4,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (3860 hom., cov: 33)
  • Exomes 𝑓: 0.22 (235 hom.)
• Consequence: LOXL1 NM_005576.4 downstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308
• Publications: 10 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 15-73952269-A-G is Benign according to our data. Variant chr15-73952269-A-G is described in ClinVar as Benign. ClinVar VariationId is 1266506.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.*432A>G		downstream_gene_variant		ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.*432A>G		downstream_gene_variant			XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.*432A>G		downstream_gene_variant		1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000562548.1	n.*132A>G		downstream_gene_variant		2
LOXL1	ENST00000567675.1	n.*133A>G		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33425 AN: 151978 Hom.: 3847 Cov.: 33

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.211

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.290

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.185

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.216 AC: 2003 AN: 9292 Hom.: 235 AF XY: 0.206 AC XY: 985 AN XY: 4772

African (AFR) AF: 0.226 AC: 99 AN: 438

American (AMR) AF: 0.167 AC: 41 AN: 246

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 76 AN: 384

East Asian (EAS) AF: 0.314 AC: 164 AN: 522

South Asian (SAS) AF: 0.412 AC: 33 AN: 80

European-Finnish (FIN) AF: 0.185 AC: 65 AN: 352

Middle Eastern (MID) AF: 0.293 AC: 17 AN: 58

European-Non Finnish (NFE) AF: 0.206 AC: 1348 AN: 6540

Other (OTH) AF: 0.238 AC: 160 AN: 672

GnomAD4 genome AF: 0.220 AC: 33470 AN: 152096 Hom.: 3860 Cov.: 33 AF XY: 0.223 AC XY: 16561 AN XY: 74344

African (AFR) AF: 0.232 AC: 9633 AN: 41522

American (AMR) AF: 0.171 AC: 2609 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3470

East Asian (EAS) AF: 0.290 AC: 1491 AN: 5134

South Asian (SAS) AF: 0.386 AC: 1863 AN: 4832

European-Finnish (FIN) AF: 0.185 AC: 1958 AN: 10598

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14270 AN: 67930

Other (OTH) AF: 0.246 AC: 518 AN: 2106

Alfa AF: 0.214 Hom.: 6566

Bravo AF: 0.217

Asia WGS AF: 0.363 AC: 1263 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Oct 16, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30986821) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.35
PhyloP100		0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7173049; hg19: chr15-74244610;