chr5-122077761-G-C

Position:

chr5-122077761-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002317.7(LOX):c.225C>G(p.Ala75Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00302 in 1,552,762 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0038 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 126 hom. )

Consequence

LOX
NM_002317.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0110

Variant links:

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]

LOX links:

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]

SRFBP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 5-122077761-G-C is Benign according to our data. Variant chr5-122077761-G-C is described in ClinVar as [Benign]. Clinvar id is 496150.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.011 with no splicing effect.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOX	NM_002317.7 linkuse as main transcript	c.225C>G	p.Ala75Ala	synonymous_variant	1/7	ENST00000231004.5	NP_002308.2	P28300D0PNI2
SRFBP1	XM_017009111.3 linkuse as main transcript	c.*2436G>C		3_prime_UTR_variant	8/8		XP_016864600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOX	ENST00000231004.5 linkuse as main transcript	c.225C>G	p.Ala75Ala	synonymous_variant	1/7	1	NM_002317.7	ENSP00000231004.4		P28300
LOX	ENST00000639739.2 linkuse as main transcript	n.225C>G		non_coding_transcript_exon_variant	1/6	5		ENSP00000492324.2		A0A7P0SNB0

Frequencies

GnomAD3 genomes

AF:

0.00382

AC:

581

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0162

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0451

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.0117

AC:

1712

AN:

146686

Hom.:

AF XY:

0.00995

AC XY:

804

AN XY:

80802

show subpopulations

Gnomad AFR exome

AF:

0.00102

Gnomad AMR exome

AF:

0.0377

Gnomad ASJ exome

AF:

0.000731

Gnomad EAS exome

AF:

0.0553

Gnomad SAS exome

AF:

0.00106

Gnomad FIN exome

AF:

0.00556

Gnomad NFE exome

AF:

0.000515

Gnomad OTH exome

AF:

0.00334

GnomAD4 exome

AF:

0.00294

AC:

4111

AN:

1400552

Hom.:

126

Cov.:

AF XY:

0.00280

AC XY:

1942

AN XY:

692438

show subpopulations

Gnomad4 AFR exome

AF:

0.000502

Gnomad4 AMR exome

AF:

0.0328

Gnomad4 ASJ exome

AF:

0.000437

Gnomad4 EAS exome

AF:

0.0602

Gnomad4 SAS exome

AF:

0.00114

Gnomad4 FIN exome

AF:

0.00394

Gnomad4 NFE exome

AF:

0.000259

Gnomad4 OTH exome

AF:

0.00249

GnomAD4 genome

AF:

0.00380

AC:

579

AN:

152210

Hom.:

Cov.:

AF XY:

0.00472

AC XY:

351

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.0160

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0453

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00184

Hom.:

Bravo

AF:

0.00593

Asia WGS

AF:

0.0150

AC:

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Jul 17, 2017	Variant summary: The LOX c.225C>G (p.Ala75Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. Mutation taster predicts a damaging outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 234/21640 control chromosomes (7 homozygotes) from ExAC at a frequency of 0.0108133, which is approximately 649 times the estimated maximal expected allele frequency of a pathogenic LOX variant (0.0000167), strongly indicating this variant is likely a benign polymorphism. Taken together, this variant is classified as benign. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 09, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

Aortic aneurysm, familial thoracic 10

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 08, 2023

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Feb 08, 2023

- -

Cardiovascular phenotype

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 13, 2019

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

3.0

DANN

Benign

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over