11-8253580-G-A

Variant names:

• chr11-8253580-G-A
• rs4237769
• NM_002315.3:c.25+9758C>T

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+9758C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,934 control chromosomes in the GnomAD database, including 9,372 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 0.32 (9372 hom., cov: 31)
• Consequence: LMO1 NM_002315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO1	NM_002315.3	MANE Select	c.25+9758C>T		intron	N/A	NP_002306.1	P25800-1
	LMO1	NM_001270428.2		c.22+14847C>T		intron	N/A	NP_001257357.1	P25800-2
	LMO1	NR_073006.2		n.541+9758C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LMO1	ENST00000335790.8	TSL:1 MANE Select	c.25+9758C>T		intron	N/A	ENSP00000338207.3	P25800-1
	LMO1	ENST00000428101.6	TSL:1	c.22+14847C>T		intron	N/A	ENSP00000404538.2	P25800-2
	LMO1	ENST00000524379.1	TSL:1	n.51+9758C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48463 AN: 151816 Hom.: 9377 Cov.: 31

Gnomad AFR AF: 0.0792

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.351

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

GnomAD4 genome AF: 0.319 AC: 48446 AN: 151934 Hom.: 9372 Cov.: 31 AF XY: 0.324 AC XY: 24079 AN XY: 74250

African (AFR) AF: 0.0789 AC: 3273 AN: 41478

American (AMR) AF: 0.387 AC: 5901 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1456 AN: 3470

East Asian (EAS) AF: 0.495 AC: 2553 AN: 5160

South Asian (SAS) AF: 0.431 AC: 2064 AN: 4790

European-Finnish (FIN) AF: 0.408 AC: 4308 AN: 10566

Middle Eastern (MID) AF: 0.479 AC: 140 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27587 AN: 67898

Other (OTH) AF: 0.350 AC: 739 AN: 2114

Alfa AF: 0.377 Hom.: 25778

Bravo AF: 0.309

Asia WGS AF: 0.402 AC: 1395 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.82
PhyloP100		-0.070
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: rs4237769; hg19: chr11-8275127;