5-122066589-T-C

Position:

• chr5-122066589-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_002317.7(LOX):​c.*154A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0329 in 570,426 control chromosomes in the GnomAD database, including 413 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (95 hom., cov: 32)
  • Exomes 𝑓: 0.034 (318 hom.)
• Consequence: LOX NM_002317.7 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.237

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-122066589-T-C is Benign according to our data. Variant chr5-122066589-T-C is described in ClinVar as [Benign]. Clinvar id is 1270158.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0285 (4341/152258) while in subpopulation NFE AF= 0.0418 (2840/67980). AF 95% confidence interval is 0.0405. There are 95 homozygotes in gnomad4. There are 2105 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 4341 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOX	NM_002317.7	c.*154A>G		3_prime_UTR_variant	7/7	ENST00000231004.5	NP_002308.2
LOX	NM_001178102.2	c.*154A>G		3_prime_UTR_variant	6/6		NP_001171573.1
LOX	NM_001317073.1	c.*154A>G		3_prime_UTR_variant	6/6		NP_001304002.1
SRFBP1	XM_017009111.3	c.1106-8726T>C		intron_variant			XP_016864600.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LOX	ENST00000231004	c.*154A>G		3_prime_UTR_variant	7/7	1	NM_002317.7	ENSP00000231004.4

Frequencies

GnomAD3 genomes AF: 0.0285 AC: 4341 AN: 152140 Hom.: 95 Cov.: 32

Gnomad AFR AF: 0.00774

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.0621

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0418

Gnomad OTH AF: 0.0282

GnomAD4 exome AF: 0.0345 AC: 14409 AN: 418168 Hom.: 318 Cov.: 5 AF XY: 0.0338 AC XY: 7418 AN XY: 219420

Gnomad4 AFR exome AF: 0.00822

Gnomad4 AMR exome AF: 0.0199

Gnomad4 ASJ exome AF: 0.0290

Gnomad4 EAS exome AF: 0.0000316

Gnomad4 SAS exome AF: 0.00803

Gnomad4 FIN exome AF: 0.0582

Gnomad4 NFE exome AF: 0.0410

Gnomad4 OTH exome AF: 0.0337

GnomAD4 genome AF: 0.0285 AC: 4341 AN: 152258 Hom.: 95 Cov.: 32 AF XY: 0.0283 AC XY: 2105 AN XY: 74444

Gnomad4 AFR AF: 0.00772

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.0621

Gnomad4 NFE AF: 0.0418

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0369 Hom.: 111

Bravo AF: 0.0255

Asia WGS AF: 0.00722 AC: 26 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.87

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

Other links and lift over

dbSNP: rs17352251; hg19: chr5-121402284;