chr11-8248697-T-C

Variant names:

• chr11-8248697-T-C
• rs3794012
• NM_002315.3:c.25+14641A>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.25+14641A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.33 in 152,202 control chromosomes in the GnomAD database, including 9,709 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 0.33 (9709 hom., cov: 34)
• Consequence: LMO1 NM_002315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 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.25+14641A>G		intron	N/A	NP_002306.1
	LMO1	NM_001270428.2		c.23-18193A>G		intron	N/A	NP_001257357.1
	LMO1	NR_073006.2		n.541+14641A>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.25+14641A>G		intron	N/A	ENSP00000338207.3
	LMO1	ENST00000428101.6	TSL:1	c.23-18193A>G		intron	N/A	ENSP00000404538.2
	LMO1	ENST00000524379.1	TSL:1	n.51+14641A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50182 AN: 152084 Hom.: 9714 Cov.: 34

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.467

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.359

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

GnomAD4 genome AF: 0.330 AC: 50167 AN: 152202 Hom.: 9709 Cov.: 34 AF XY: 0.336 AC XY: 24962 AN XY: 74402

African (AFR) AF: 0.105 AC: 4374 AN: 41552

American (AMR) AF: 0.413 AC: 6328 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1430 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2643 AN: 5178

South Asian (SAS) AF: 0.452 AC: 2174 AN: 4814

European-Finnish (FIN) AF: 0.392 AC: 4146 AN: 10590

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.408 AC: 27750 AN: 67976

Other (OTH) AF: 0.357 AC: 755 AN: 2114

Alfa AF: 0.393 Hom.: 19986

Bravo AF: 0.322

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.50
PhyloP100		-0.24
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: rs3794012; hg19: chr11-8270244;