rs10040971

Positions:

• chr5-122069092-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002317.7(LOX):​c.1247+961A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0987 in 152,132 control chromosomes in the GnomAD database, including 947 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.099 (947 hom., cov: 32)
• Consequence: LOX NM_002317.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.321

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOX	NM_002317.7	c.1247+961A>G		intron_variant		ENST00000231004.5
LOX	NM_001178102.2	c.557+961A>G		intron_variant
LOX	NM_001317073.1	c.356+961A>G		intron_variant
SRFBP1	XM_017009111.3	c.1106-6223T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LOX	ENST00000231004.5	c.1247+961A>G		intron_variant		1	NM_002317.7	P1

Frequencies

GnomAD3 genomes AF: 0.0988 AC: 15017 AN: 152014 Hom.: 946 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.0209

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0376

Gnomad SAS AF: 0.142

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.118

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0987 AC: 15014 AN: 152132 Hom.: 947 Cov.: 32 AF XY: 0.0971 AC XY: 7224 AN XY: 74360

Gnomad4 AFR AF: 0.0268

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.0381

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.117

Alfa AF: 0.132 Hom.: 884

Bravo AF: 0.0923

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.53

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: rs10040971; hg19: chr5-121404787;