chr12-16589453-C-G

Variant names:

• chr12-16589453-C-G
• rs2058797
• NM_018640.5:c.206+11202G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243613.1(LMO3):​c.272+4684G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 152,064 control chromosomes in the GnomAD database, including 60,635 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 0.87 (60635 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: LMO3 NM_001243613.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• Publications: 0 publications found

Genes affected

LMO3 (HGNC:6643): (LIM domain only 3) The protein encoded by this gene belongs to the rhombotin family of cysteine-rich LIM domain oncogenes. This gene is predominantly expressed in the brain. Related family members, LMO1 and LMO2 on chromosome 11, have been reported to be involved in chromosomal translocations in T-cell leukemia. Many alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

MGST1 (HGNC:7061): (microsomal glutathione S-transferase 1) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, two of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. Other family members, demonstrating glutathione S-transferase and peroxidase activities, are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. This gene encodes a protein that catalyzes the conjugation of glutathione to electrophiles and the reduction of lipid hydroperoxides. This protein is localized to the endoplasmic reticulum and outer mitochondrial membrane where it is thought to protect these membranes from oxidative stress. Several transcript variants, some non-protein coding and some protein coding, have been found for this gene. [provided by RefSeq, May 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.987 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243613.1. 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
	LMO3	NM_018640.5	MANE Select	c.206+11202G>C		intron	N/A	NP_061110.2
	LMO3	NM_001243613.1		c.272+4684G>C		intron	N/A	NP_001230542.1
	LMO3	NM_001243612.1		c.260+11202G>C		intron	N/A	NP_001230541.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO3	ENST00000537304.6	TSL:1 MANE Select	c.206+11202G>C		intron	N/A	ENSP00000440099.1
	LMO3	ENST00000261169.10	TSL:1	c.239+11202G>C		intron	N/A	ENSP00000261169.6
	LMO3	ENST00000320122.10	TSL:1	c.206+11202G>C		intron	N/A	ENSP00000312856.6

Frequencies

GnomAD3 genomes AF: 0.874 AC: 132874 AN: 151946 Hom.: 60616 Cov.: 31

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.969

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.978

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.911

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.902

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

GnomAD4 genome AF: 0.874 AC: 132943 AN: 152064 Hom.: 60635 Cov.: 31 AF XY: 0.879 AC XY: 65355 AN XY: 74368

African (AFR) AF: 0.581 AC: 24037 AN: 41404

American (AMR) AF: 0.944 AC: 14410 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.969 AC: 3363 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5147 AN: 5154

South Asian (SAS) AF: 0.978 AC: 4723 AN: 4828

European-Finnish (FIN) AF: 0.999 AC: 10602 AN: 10614

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.994 AC: 67583 AN: 68010

Other (OTH) AF: 0.902 AC: 1904 AN: 2110

Alfa AF: 0.926 Hom.: 7956

Bravo AF: 0.858

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.14
DANN	Benign	0.46
PhyloP100		-1.2
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: rs2058797; hg19: chr12-16742387;