rs2288393

Variant names:

• chr5-122077195-C-G
• rs2288393
• NM_002317.7:c.631+160G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-122077195-C-G
• chr5-122077195-C-A

Variant summary

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

The NM_001178102.2(LOX):​c.-253G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,468,378 control chromosomes in the GnomAD database, including 19,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.14 (1694 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17680 hom.)
• Consequence: LOX NM_001178102.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.145
• Publications: 21 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=-0.66).
• BP6: Variant 5-122077195-C-G is Benign according to our data. Variant chr5-122077195-C-G is described in ClinVar as Benign. ClinVar VariationId is 1288647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178102.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOX	NM_002317.7	MANE Select	c.631+160G>C		intron	N/A	NP_002308.2
	LOX	NM_001178102.2		c.-253G>C		5_prime_UTR	Exon 1 of 6	NP_001171573.1	B7ZAJ4
	LOX	NM_001317073.1		c.-255G>C		upstream_gene	N/A	NP_001304002.1	B0AZT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOX	ENST00000231004.5	TSL:1 MANE Select	c.631+160G>C		intron	N/A	ENSP00000231004.4	P28300
	LOX	ENST00000503759.5	TSL:2	c.-253G>C		5_prime_UTR	Exon 1 of 6	ENSP00000503423.1	B7ZAJ4
	LOX	ENST00000939087.1		c.631+160G>C		intron	N/A	ENSP00000609146.1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21603 AN: 151942 Hom.: 1693 Cov.: 32

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.166

GnomAD4 exome AF: 0.162 AC: 213775 AN: 1316318 Hom.: 17680 Cov.: 33 AF XY: 0.162 AC XY: 104307 AN XY: 642000

African (AFR) AF: 0.0904 AC: 2660 AN: 29426

American (AMR) AF: 0.147 AC: 3817 AN: 25882

Ashkenazi Jewish (ASJ) AF: 0.160 AC: 3199 AN: 20054

East Asian (EAS) AF: 0.128 AC: 4527 AN: 35336

South Asian (SAS) AF: 0.154 AC: 10255 AN: 66570

European-Finnish (FIN) AF: 0.130 AC: 4452 AN: 34352

Middle Eastern (MID) AF: 0.175 AC: 650 AN: 3710

European-Non Finnish (NFE) AF: 0.168 AC: 175324 AN: 1046398

Other (OTH) AF: 0.163 AC: 8891 AN: 54590

GnomAD4 genome AF: 0.142 AC: 21607 AN: 152060 Hom.: 1694 Cov.: 32 AF XY: 0.139 AC XY: 10357 AN XY: 74320

African (AFR) AF: 0.0942 AC: 3912 AN: 41508

American (AMR) AF: 0.163 AC: 2500 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 576 AN: 3470

East Asian (EAS) AF: 0.146 AC: 747 AN: 5122

South Asian (SAS) AF: 0.146 AC: 705 AN: 4814

European-Finnish (FIN) AF: 0.125 AC: 1317 AN: 10574

Middle Eastern (MID) AF: 0.139 AC: 41 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11434 AN: 67970

Other (OTH) AF: 0.164 AC: 346 AN: 2104

Alfa AF: 0.0749 Hom.: 94

Bravo AF: 0.145

Asia WGS AF: 0.108 AC: 376 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	17
DANN	Benign	0.85
PhyloP100		0.14
PromoterAI		-0.013	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2288393; hg19: chr5-121412890; COSMIC: COSV50237110; COSMIC: COSV50237110;