rs453061

Variant names:

• chr11-8249329-A-G
• rs453061
• NM_002315.3:c.25+14009T>C

Variant summary

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

The NM_002315.3(LMO1):​c.25+14009T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.961 in 152,236 control chromosomes in the GnomAD database, including 70,478 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 0.96 (70478 hom., cov: 31)
• Consequence: LMO1 NM_002315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.796
• Publications: 2 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 -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 = 0.981 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO1	NM_002315.3	c.25+14009T>C		intron_variant	Intron 1 of 3	ENST00000335790.8	NP_002306.1
LMO1	NM_001270428.2	c.23-18825T>C		intron_variant	Intron 1 of 3		NP_001257357.1
LMO1	NR_073006.2	n.541+14009T>C		intron_variant	Intron 1 of 3
LMO1	XM_011520099.3	c.-9+13429T>C		intron_variant	Intron 1 of 3		XP_011518401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO1	ENST00000335790.8	c.25+14009T>C		intron_variant	Intron 1 of 3	1	NM_002315.3	ENSP00000338207.3
LMO1	ENST00000428101.6	c.23-18825T>C		intron_variant	Intron 1 of 3	1		ENSP00000404538.2
LMO1	ENST00000524379.1	n.51+14009T>C		intron_variant	Intron 1 of 3	1
LMO1	ENST00000534484.1	c.-9+14343T>C		intron_variant	Intron 1 of 3	5		ENSP00000435456.1

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146246 AN: 152118 Hom.: 70434 Cov.: 31

Gnomad AFR AF: 0.897

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.978

Gnomad ASJ AF: 0.978

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.963

Gnomad FIN AF: 0.998

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.987

Gnomad OTH AF: 0.965

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

GnomAD4 genome AF: 0.961 AC: 146347 AN: 152236 Hom.: 70478 Cov.: 31 AF XY: 0.963 AC XY: 71674 AN XY: 74452

African (AFR) AF: 0.897 AC: 37227 AN: 41512

American (AMR) AF: 0.978 AC: 14955 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.978 AC: 3397 AN: 3472

East Asian (EAS) AF: 0.993 AC: 5138 AN: 5174

South Asian (SAS) AF: 0.963 AC: 4644 AN: 4822

European-Finnish (FIN) AF: 0.998 AC: 10590 AN: 10612

Middle Eastern (MID) AF: 0.976 AC: 287 AN: 294

European-Non Finnish (NFE) AF: 0.987 AC: 67158 AN: 68032

Other (OTH) AF: 0.965 AC: 2039 AN: 2112

Alfa AF: 0.973 Hom.: 104543

Bravo AF: 0.958

Asia WGS AF: 0.943 AC: 3281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.19
DANN	Benign	0.47
PhyloP100		-0.80
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: rs453061; hg19: chr11-8270876;