rs3794012

Positions:

• chr11-8248697-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000335790.8(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 ENST00000335790.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.242

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMO1	NM_002315.3	c.25+14641A>G		intron_variant		ENST00000335790.8	NP_002306.1
LMO1	NM_001270428.2	c.23-18193A>G		intron_variant			NP_001257357.1
LMO1	XM_011520099.3	c.-9+14061A>G		intron_variant			XP_011518401.1
LMO1	NR_073006.2	n.541+14641A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMO1	ENST00000335790.8	c.25+14641A>G		intron_variant		1	NM_002315.3	ENSP00000338207	A1
LMO1	ENST00000428101.6	c.23-18193A>G		intron_variant		1		ENSP00000404538	P4
LMO1	ENST00000524379.1	n.51+14641A>G		intron_variant, non_coding_transcript_variant		1
LMO1	ENST00000534484.1	c.-9+14975A>G		intron_variant		5		ENSP00000435456

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

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.392

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.357

Alfa AF: 0.401 Hom.: 16454

Bravo AF: 0.322

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs3794012; hg19: chr11-8270244;