5-122073485-G-C

Variant names:

• chr5-122073485-G-C
• rs2956540
• NM_002317.7:c.1035+528C>G

Variant summary

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

The NM_002317.7(LOX):​c.1035+528C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,974 control chromosomes in the GnomAD database, including 12,881 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 0.41 (12881 hom., cov: 33)
• Consequence: LOX NM_002317.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.656
• Publications: 25 publications found

Genes affected

LOX (HGNC:6664): (lysyl oxidase) This gene encodes a member of the lysyl oxidase family of proteins. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate a regulatory propeptide and the mature enzyme. The copper-dependent amine oxidase activity of this enzyme functions in the crosslinking of collagens and elastin, while the propeptide may play a role in tumor suppression. In addition, defects in this gene have been linked with predisposition to thoracic aortic aneurysms and dissections. [provided by RefSeq, Jul 2016]

SRFBP1 (HGNC:26333): (serum response factor binding protein 1) Enables RNA binding activity. Predicted to be involved in maturation of SSU-rRNA. Predicted to be located in perinuclear region of cytoplasm. Predicted to be part of 90S preribosome. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOX	NM_002317.7	c.1035+528C>G		intron_variant	Intron 4 of 6	ENST00000231004.5	NP_002308.2
LOX	NM_001178102.2	c.345+528C>G		intron_variant	Intron 3 of 5		NP_001171573.1
LOX	NM_001317073.1	c.144+528C>G		intron_variant	Intron 3 of 5		NP_001304002.1
SRFBP1	XM_017009111.3	c.1106-1830G>C		intron_variant	Intron 7 of 7		XP_016864600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOX	ENST00000231004.5	c.1035+528C>G		intron_variant	Intron 4 of 6	1	NM_002317.7	ENSP00000231004.4

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61671 AN: 151856 Hom.: 12861 Cov.: 33

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.398

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

GnomAD4 genome AF: 0.406 AC: 61735 AN: 151974 Hom.: 12881 Cov.: 33 AF XY: 0.408 AC XY: 30282 AN XY: 74286

African (AFR) AF: 0.358 AC: 14834 AN: 41418

American (AMR) AF: 0.349 AC: 5332 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1447 AN: 3468

East Asian (EAS) AF: 0.263 AC: 1360 AN: 5168

South Asian (SAS) AF: 0.379 AC: 1824 AN: 4812

European-Finnish (FIN) AF: 0.544 AC: 5748 AN: 10560

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29982 AN: 67952

Other (OTH) AF: 0.397 AC: 837 AN: 2110

Alfa AF: 0.301 Hom.: 822

Bravo AF: 0.392

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.52
PhyloP100		-0.66
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: rs2956540; hg19: chr5-121409180; COSMIC: COSV50237098;