rs2168101

Variant names:

• chr11-8233861-C-A
• rs2168101
• NM_002315.3:c.26-3357G>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6 BA1

The NM_002315.3(LMO1):​c.26-3357G>T variant causes a intron change. The variant allele was found at a frequency of 0.238 in 152,076 control chromosomes in the GnomAD database, including 5,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign,protective (no stars).

• Frequency: Genomes: 𝑓 0.24 (5286 hom., cov: 32)
• Consequence: LMO1 NM_002315.3 intron
• Clinical Significance: Benign; protective no assertion criteria provided B:2
• Conservation: PhyloP100: 5.03
• Publications: 56 publications found

Genes affected

LMO1 (HGNC:6641): (LIM domain only 1) This locus encodes a transcriptional regulator that contains two cysteine-rich LIM domains but lacks a DNA-binding domain. LIM domains may play a role in protein interactions; thus the encoded protein may regulate transcription by competitively binding to specific DNA-binding transcription factors. Alterations at this locus have been associated with acute lymphoblastic T-cell leukemia. Chromosomal rearrangements have been observed between this locus and at least two loci, the delta subunit of the T-cell antigen receptor gene and the LIM domain binding 1 gene. Alternatively spliced transcript variants have been described. [provided by RefSeq, Jul 2012]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 11-8233861-C-A is Benign according to our data. Variant chr11-8233861-C-A is described in ClinVar as Benign|protective. ClinVar VariationId is 221554.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002315.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO1	NM_002315.3	MANE Select	c.26-3357G>T		intron	N/A	NP_002306.1
	LMO1	NM_001270428.2		c.23-3357G>T		intron	N/A	NP_001257357.1
	LMO1	NR_073006.2		n.542-3357G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO1	ENST00000335790.8	TSL:1 MANE Select	c.26-3357G>T		intron	N/A	ENSP00000338207.3
	LMO1	ENST00000428101.6	TSL:1	c.23-3357G>T		intron	N/A	ENSP00000404538.2
	LMO1	ENST00000524379.1	TSL:1	n.52-3357G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36177 AN: 151958 Hom.: 5286 Cov.: 32

Gnomad AFR AF: 0.0579

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.285

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.238 AC: 36168 AN: 152076 Hom.: 5286 Cov.: 32 AF XY: 0.244 AC XY: 18136 AN XY: 74324

African (AFR) AF: 0.0577 AC: 2396 AN: 41492

American (AMR) AF: 0.296 AC: 4524 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3472

East Asian (EAS) AF: 0.285 AC: 1470 AN: 5160

South Asian (SAS) AF: 0.255 AC: 1227 AN: 4812

European-Finnish (FIN) AF: 0.396 AC: 4179 AN: 10566

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.305 AC: 20722 AN: 67970

Other (OTH) AF: 0.212 AC: 448 AN: 2110

Alfa AF: 0.283 Hom.: 9969

Bravo AF: 0.223

Asia WGS AF: 0.220 AC: 767 AN: 3478

ClinVar

Significance: Benign; protective

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

LMO1 POLYMORPHISM Benign:1

Jan 07, 2025

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

Neuroblastoma, susceptibility to, 7 Benign:1

ClinVar Staff, National Center for Biotechnology Information (NCBI)

Significance: protective

Review Status: no assertion criteria provided

Collection Method: literature only

Oldridge et al., 2015 (PubMed 26560027) state that the SNP rs2168101 G>T is the most highly associated variant (combined P = 7.47 × 10(-29), odds ratio 0.65, 95% confidence interval 0.60-0.70), and resides in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G allele that is associated with tumour formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P = 0.028) in neuroblastoma primary tumours, and ablates GATA3 binding."

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Benign	0.84
PhyloP100		5.0
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: rs2168101; hg19: chr11-8255408;