11-8243510-T-C

Variant names:

• chr11-8243510-T-C
• rs376813
• NM_002315.3:c.26-13006A>G

Variant summary

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

The NM_002315.3(LMO1):​c.26-13006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.963 in 152,256 control chromosomes in the GnomAD database, including 70,631 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 (70631 hom., cov: 32)
• Consequence: LMO1 NM_002315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.26-13006A>G		intron	N/A	NP_002306.1
	LMO1	NM_001270428.2		c.23-13006A>G		intron	N/A	NP_001257357.1
	LMO1	NR_073006.2		n.542-13006A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO1	ENST00000335790.8	TSL:1 MANE Select	c.26-13006A>G		intron	N/A	ENSP00000338207.3
	LMO1	ENST00000428101.6	TSL:1	c.23-13006A>G		intron	N/A	ENSP00000404538.2
	LMO1	ENST00000524379.1	TSL:1	n.52-13006A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.963 AC: 146515 AN: 152138 Hom.: 70574 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.969

Gnomad AMR AF: 0.970

Gnomad ASJ AF: 0.916

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.930

Gnomad NFE AF: 0.954

Gnomad OTH AF: 0.960

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

GnomAD4 genome AF: 0.963 AC: 146631 AN: 152256 Hom.: 70631 Cov.: 32 AF XY: 0.966 AC XY: 71871 AN XY: 74426

African (AFR) AF: 0.968 AC: 40231 AN: 41544

American (AMR) AF: 0.970 AC: 14846 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.916 AC: 3175 AN: 3468

East Asian (EAS) AF: 0.999 AC: 5159 AN: 5162

South Asian (SAS) AF: 0.976 AC: 4700 AN: 4818

European-Finnish (FIN) AF: 0.984 AC: 10457 AN: 10626

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.954 AC: 64872 AN: 68012

Other (OTH) AF: 0.961 AC: 2033 AN: 2116

Alfa AF: 0.958 Hom.: 64783

Bravo AF: 0.962

Asia WGS AF: 0.982 AC: 3416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.6
DANN	Benign	0.84
PhyloP100		0.35
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: rs376813; hg19: chr11-8265057;