rs3792803

Variant names:

• chr5-122073788-A-G
• rs3792803
• NM_002317.7:c.1035+225T>C

Variant summary

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

The NM_002317.7(LOX):​c.1035+225T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0223 in 152,260 control chromosomes in the GnomAD database, including 101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.022 (101 hom., cov: 33)
• Consequence: LOX NM_002317.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0490
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 5-122073788-A-G is Benign according to our data. Variant chr5-122073788-A-G is described in ClinVar as Benign. ClinVar VariationId is 1181166.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOX	NM_002317.7	c.1035+225T>C		intron_variant	Intron 4 of 6	ENST00000231004.5	NP_002308.2
LOX	NM_001178102.2	c.345+225T>C		intron_variant	Intron 3 of 5		NP_001171573.1
LOX	NM_001317073.1	c.144+225T>C		intron_variant	Intron 3 of 5		NP_001304002.1
SRFBP1	XM_017009111.3	c.1106-1527A>G		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+225T>C		intron_variant	Intron 4 of 6	1	NM_002317.7	ENSP00000231004.4

Frequencies

GnomAD3 genomes AF: 0.0223 AC: 3388 AN: 152142 Hom.: 100 Cov.: 33

Gnomad AFR AF: 0.0612

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.0459

Gnomad SAS AF: 0.0312

Gnomad FIN AF: 0.00405

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.0162

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

GnomAD4 genome AF: 0.0223 AC: 3403 AN: 152260 Hom.: 101 Cov.: 33 AF XY: 0.0223 AC XY: 1660 AN XY: 74452

African (AFR) AF: 0.0613 AC: 2546 AN: 41524

American (AMR) AF: 0.0229 AC: 350 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.0460 AC: 238 AN: 5176

South Asian (SAS) AF: 0.0313 AC: 151 AN: 4830

European-Finnish (FIN) AF: 0.00405 AC: 43 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68022

Other (OTH) AF: 0.0175 AC: 37 AN: 2116

Alfa AF: 0.0297 Hom.: 51

Bravo AF: 0.0260

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 22, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.74
PhyloP100		0.049
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3792803; hg19: chr5-121409483; COSMIC: COSV50239176;