rs204938

Variant names:

• chr11-8256650-C-T
• rs204938
• NM_002315.3:c.25+6688G>A

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+6688G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.494 in 152,104 control chromosomes in the GnomAD database, including 20,116 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 0.49 (20116 hom., cov: 33)
• Consequence: LMO1 NM_002315.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 19 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO1	NM_002315.3	c.25+6688G>A		intron_variant	Intron 1 of 3	ENST00000335790.8	NP_002306.1
LMO1	NM_001270428.2	c.22+11777G>A		intron_variant	Intron 1 of 3		NP_001257357.1
LMO1	NR_073006.2	n.541+6688G>A		intron_variant	Intron 1 of 3
LMO1	XM_011520099.3	c.-9+6108G>A		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+6688G>A		intron_variant	Intron 1 of 3	1	NM_002315.3	ENSP00000338207.3
LMO1	ENST00000428101.6	c.22+11777G>A		intron_variant	Intron 1 of 3	1		ENSP00000404538.2
LMO1	ENST00000524379.1	n.51+6688G>A		intron_variant	Intron 1 of 3	1
LMO1	ENST00000534484.1	c.-9+7022G>A		intron_variant	Intron 1 of 3	5		ENSP00000435456.1

Frequencies

GnomAD3 genomes AF: 0.494 AC: 75053 AN: 151986 Hom.: 20123 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.565

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.791

Gnomad SAS AF: 0.589

Gnomad FIN AF: 0.592

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.494 AC: 75066 AN: 152104 Hom.: 20116 Cov.: 33 AF XY: 0.503 AC XY: 37416 AN XY: 74352

African (AFR) AF: 0.278 AC: 11515 AN: 41474

American (AMR) AF: 0.582 AC: 8896 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3468

East Asian (EAS) AF: 0.790 AC: 4088 AN: 5174

South Asian (SAS) AF: 0.588 AC: 2836 AN: 4826

European-Finnish (FIN) AF: 0.592 AC: 6257 AN: 10562

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37595 AN: 67996

Other (OTH) AF: 0.526 AC: 1111 AN: 2114

Alfa AF: 0.540 Hom.: 37226

Bravo AF: 0.484

Asia WGS AF: 0.613 AC: 2130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.9
DANN	Benign	0.43
PhyloP100		-0.0090
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: rs204938; hg19: chr11-8278197;