rs3740616

Positions:

• chr11-33859350-T-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_005574.4(LMO2):​c.*6A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,604,886 control chromosomes in the GnomAD database, including 37,846 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.18 (2734 hom., cov: 32)
  • Exomes 𝑓: 0.22 (35112 hom.)
• Consequence: LMO2 NM_005574.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

Genes affected

LMO2 (HGNC:6642): (LIM domain only 2) LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Nov 2008]

LMO2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP6: Variant 11-33859350-T-A is Benign according to our data. Variant chr11-33859350-T-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMO2	NM_005574.4	c.*6A>T		3_prime_UTR_variant	6/6	ENST00000257818.3	NP_005565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818	c.*6A>T		3_prime_UTR_variant	6/6	1	NM_005574.4	ENSP00000257818.2

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27489 AN: 151980 Hom.: 2732 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.186

GnomAD3 exomes AF: 0.189 AC: 47270 AN: 250068 Hom.: 4878 AF XY: 0.194 AC XY: 26157 AN XY: 135064

Gnomad AFR exome AF: 0.0999

Gnomad AMR exome AF: 0.118

Gnomad ASJ exome AF: 0.221

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.178

Gnomad FIN exome AF: 0.242

Gnomad NFE exome AF: 0.226

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.217 AC: 315064 AN: 1452788 Hom.: 35112 Cov.: 29 AF XY: 0.217 AC XY: 156655 AN XY: 722244

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.180

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.206

GnomAD4 genome AF: 0.181 AC: 27499 AN: 152098 Hom.: 2734 Cov.: 32 AF XY: 0.182 AC XY: 13516 AN XY: 74338

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.162

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.177

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.184

Alfa AF: 0.214 Hom.: 1235

Bravo AF: 0.173

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.44
DANN	Benign	0.63

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: rs3740616; hg19: chr11-33880896; COSMIC: COSV57648055;