chr5-122069092-T-C

Variant names:

• chr5-122069092-T-C
• rs10040971
• NM_002317.7:c.1247+961A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 -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.

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.1247+961A>G		intron	N/A	NP_002308.2
	LOX	NM_001178102.2		c.557+961A>G		intron	N/A	NP_001171573.1	B7ZAJ4
	LOX	NM_001317073.1		c.356+961A>G		intron	N/A	NP_001304002.1	B0AZT2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LOX	ENST00000231004.5	TSL:1 MANE Select	c.1247+961A>G		intron	N/A	ENSP00000231004.4	P28300
	LOX	ENST00000513319.5	TSL:1	c.356+961A>G		intron	N/A	ENSP00000503104.1	B0AZT2
	LOX	ENST00000939087.1		c.1247+961A>G		intron	N/A	ENSP00000609146.1

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

African (AFR) AF: 0.0268 AC: 1114 AN: 41552

American (AMR) AF: 0.105 AC: 1609 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 511 AN: 3468

East Asian (EAS) AF: 0.0381 AC: 197 AN: 5176

South Asian (SAS) AF: 0.142 AC: 682 AN: 4818

European-Finnish (FIN) AF: 0.114 AC: 1205 AN: 10584

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9399 AN: 67938

Other (OTH) AF: 0.117 AC: 247 AN: 2116

Alfa AF: 0.133 Hom.: 1238

Bravo AF: 0.0923

Asia WGS AF: 0.0720 AC: 248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.2
DANN	Benign	0.53
PhyloP100		0.32
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: rs10040971; hg19: chr5-121404787;