rs10519694

Variant names:

• chr5-122071524-C-T
• rs10519694
• NM_002317.7:c.1036-935G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 28 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=-0.79).
• 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 rank	MANE	Protein	UniProt
LOX	NM_002317.7	c.1036-935G>A		intron_variant	Intron 4 of 6	ENST00000231004.5	NP_002308.2
LOX	NM_001178102.2	c.346-935G>A		intron_variant	Intron 3 of 5		NP_001171573.1
LOX	NM_001317073.1	c.145-935G>A		intron_variant	Intron 3 of 5		NP_001304002.1
SRFBP1	XM_017009111.3	c.1106-3791C>T		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.1036-935G>A		intron_variant	Intron 4 of 6	1	NM_002317.7	ENSP00000231004.4

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

African (AFR) AF: 0.0949 AC: 3937 AN: 41502

American (AMR) AF: 0.144 AC: 2200 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.213 AC: 739 AN: 3472

East Asian (EAS) AF: 0.0688 AC: 356 AN: 5178

South Asian (SAS) AF: 0.194 AC: 933 AN: 4816

European-Finnish (FIN) AF: 0.408 AC: 4299 AN: 10542

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

European-Non Finnish (NFE) AF: 0.261 AC: 17716 AN: 67948

Other (OTH) AF: 0.182 AC: 385 AN: 2116

Alfa AF: 0.244 Hom.: 2900

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
PhyloP100		-0.59
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: rs10519694; hg19: chr5-121407219;