5-122077513-C-T

Variant names:

• chr5-122077513-C-T
• rs1800449
• NM_002317.7:c.473G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002317.7(LOX):​c.473G>A​(p.Arg158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,613,690 control chromosomes in the GnomAD database, including 23,736 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.17 (2280 hom., cov: 33)
  • Exomes 𝑓: 0.17 (21456 hom.)
• Consequence: LOX NM_002317.7 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0900
• Publications: 117 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0011650324).
• BP6: Variant 5-122077513-C-T is Benign according to our data. Variant chr5-122077513-C-T is described in ClinVar as Benign. ClinVar VariationId is 14363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002317.7. 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.473G>A	p.Arg158Gln	missense	Exon 1 of 7	NP_002308.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOX	ENST00000231004.5	TSL:1 MANE Select	c.473G>A	p.Arg158Gln	missense	Exon 1 of 7	ENSP00000231004.4	P28300
	LOX	ENST00000939087.1		c.473G>A	p.Arg158Gln	missense	Exon 2 of 8	ENSP00000609146.1
	LOX	ENST00000639739.2	TSL:5	n.473G>A		non_coding_transcript_exon	Exon 1 of 6	ENSP00000492324.2	A0A7P0SNB0

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25752 AN: 152054 Hom.: 2278 Cov.: 33

Gnomad AFR AF: 0.170

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.185

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.160

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.172 AC: 42767 AN: 248724 AF XY: 0.172

Gnomad AFR exome AF: 0.172

Gnomad AMR exome AF: 0.181

Gnomad ASJ exome AF: 0.162

Gnomad EAS exome AF: 0.204

Gnomad FIN exome AF: 0.142

Gnomad NFE exome AF: 0.171

Gnomad OTH exome AF: 0.171

GnomAD4 exome AF: 0.170 AC: 248906 AN: 1461518 Hom.: 21456 Cov.: 34 AF XY: 0.170 AC XY: 123922 AN XY: 727082

African (AFR) AF: 0.170 AC: 5682 AN: 33480

American (AMR) AF: 0.182 AC: 8142 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 4249 AN: 26128

East Asian (EAS) AF: 0.189 AC: 7508 AN: 39698

South Asian (SAS) AF: 0.171 AC: 14726 AN: 86258

European-Finnish (FIN) AF: 0.146 AC: 7772 AN: 53110

Middle Eastern (MID) AF: 0.178 AC: 1029 AN: 5768

European-Non Finnish (NFE) AF: 0.170 AC: 189376 AN: 1111966

Other (OTH) AF: 0.173 AC: 10422 AN: 60388

GnomAD4 genome AF: 0.169 AC: 25765 AN: 152172 Hom.: 2280 Cov.: 33 AF XY: 0.166 AC XY: 12327 AN XY: 74386

African (AFR) AF: 0.170 AC: 7061 AN: 41534

American (AMR) AF: 0.184 AC: 2815 AN: 15298

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

East Asian (EAS) AF: 0.191 AC: 980 AN: 5142

South Asian (SAS) AF: 0.159 AC: 767 AN: 4822

European-Finnish (FIN) AF: 0.138 AC: 1465 AN: 10600

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11635 AN: 67992

Other (OTH) AF: 0.182 AC: 384 AN: 2108

Alfa AF: 0.169 Hom.: 9155

Bravo AF: 0.177

TwinsUK AF: 0.159 AC: 590

ALSPAC AF: 0.166 AC: 638

ESP6500AA AF: 0.178 AC: 784

ESP6500EA AF: 0.174 AC: 1494

ExAC AF: 0.170 AC: 20681

Asia WGS AF: 0.144 AC: 500 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.172

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	LOX POLYMORPHISM (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.70	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.5
DANN	Benign	0.95
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.46	T
MetaRNN	Benign	0.0012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.97	L
PhyloP100		-0.090
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.68	N
REVEL	Benign	0.048
Sift	Benign	0.54	T
Sift4G	Benign	0.75	T
Polyphen		0.0	B
Vest4		0.018
MPC		0.62
ClinPred		0.0029	T
GERP RS		2.4
PromoterAI		-0.0086	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.036
gMVP		0.38
Mutation Taster		=97/3	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: rs1800449; hg19: chr5-121413208; COSMIC: COSV50237378; COSMIC: COSV50237378;