rs2278226

Variant names:

• chr5-122077761-G-C
• rs2278226
• NM_002317.7:c.225C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-122077761-G-C
• chr5-122077761-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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 (★★). Synonymous variant affecting the same amino acid position (i.e. A75A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0038 (13 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (126 hom.)
• Consequence: LOX NM_002317.7 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.0110
• Publications: 11 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 -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 VariationId 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.

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.225C>G	p.Ala75Ala	synonymous	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.225C>G	p.Ala75Ala	synonymous	Exon 1 of 7	ENSP00000231004.4	P28300
	LOX	ENST00000939087.1		c.225C>G	p.Ala75Ala	synonymous	Exon 2 of 8	ENSP00000609146.1
	LOX	ENST00000639739.2	TSL:5	n.225C>G		non_coding_transcript_exon	Exon 1 of 6	ENSP00000492324.2	A0A7P0SNB0

Frequencies

GnomAD3 genomes AF: 0.00382 AC: 581 AN: 152102 Hom.: 13 Cov.: 32

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

GnomAD2 exomes AF: 0.0117 AC: 1712 AN: 146686 AF XY: 0.00995

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 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.: 33 AF XY: 0.00280 AC XY: 1942 AN XY: 692438

African (AFR) AF: 0.000502 AC: 16 AN: 31882

American (AMR) AF: 0.0328 AC: 1199 AN: 36594

Ashkenazi Jewish (ASJ) AF: 0.000437 AC: 11 AN: 25168

East Asian (EAS) AF: 0.0602 AC: 2206 AN: 36618

South Asian (SAS) AF: 0.00114 AC: 92 AN: 80542

European-Finnish (FIN) AF: 0.00394 AC: 158 AN: 40116

Middle Eastern (MID) AF: 0.000532 AC: 3 AN: 5636

European-Non Finnish (NFE) AF: 0.000259 AC: 281 AN: 1085710

Other (OTH) AF: 0.00249 AC: 145 AN: 58286

GnomAD4 genome AF: 0.00380 AC: 579 AN: 152210 Hom.: 13 Cov.: 32 AF XY: 0.00472 AC XY: 351 AN XY: 74410

African (AFR) AF: 0.000698 AC: 29 AN: 41550

American (AMR) AF: 0.0160 AC: 245 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.0453 AC: 232 AN: 5124

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000294 AC: 20 AN: 67992

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00184 Hom.: 0

Bravo AF: 0.00593

Asia WGS AF: 0.0150 AC: 51 AN: 3470

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Aortic aneurysm, familial thoracic 10 (1)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		-0.011
PromoterAI		-0.042	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2278226; hg19: chr5-121413456; COSMIC: COSV50237655; COSMIC: COSV50237655;