rs10519694

chr5-122071524-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002317.7(LOX):c.1036-935G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,062 control chromosomes in the GnomAD database, including 3,875 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 0.20 (3875 hom., cov: 32)
• Consequence: LOX NM_002317.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOX	NM_002317.7	c.1036-935G>A		intron_variant		ENST00000231004.5
LOX	NM_001178102.2	c.346-935G>A		intron_variant
LOX	NM_001317073.1	c.145-935G>A		intron_variant
SRFBP1	XM_017009111.3	c.1106-3791C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOX	ENST00000231004.5	c.1036-935G>A		intron_variant		1	NM_002317.7	P1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30854 AN: 151946 Hom.: 3876 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.213

Gnomad EAS AF: 0.0684

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.203 AC: 30861 AN: 152062 Hom.: 3875 Cov.: 32 AF XY: 0.208 AC XY: 15480 AN XY: 74324

Gnomad4 AFR AF: 0.0949

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.213

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.408

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.182

Alfa AF: 0.245 Hom.: 2655

Bravo AF: 0.178

Asia WGS AF: 0.152 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	2.4
Dann	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs10519694; hg19: chr5-121407219;