rs3781578

Positions:

• chr11-33885280-G-A

Variant summary

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

The NM_005574.4(LMO2):​c.-335-3393C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,076 control chromosomes in the GnomAD database, including 4,620 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 0.24 (4620 hom., cov: 32)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LMO2	NM_005574.4	c.-335-3393C>T		intron_variant		ENST00000257818.3	NP_005565.2
LMO2	XM_017017733.2	c.-264-3393C>T		intron_variant			XP_016873222.1
LMO2	XM_047426944.1	c.-433-3004C>T		intron_variant			XP_047282900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3	c.-335-3393C>T		intron_variant		1	NM_005574.4	ENSP00000257818

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36295 AN: 151958 Hom.: 4617 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.312

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.239 AC: 36319 AN: 152076 Hom.: 4620 Cov.: 32 AF XY: 0.237 AC XY: 17607 AN XY: 74330

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.269

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.311

Gnomad4 FIN AF: 0.154

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.237

Alfa AF: 0.261 Hom.: 7016

Bravo AF: 0.246

Asia WGS AF: 0.295 AC: 1026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.032
DANN	Benign	0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3781578; hg19: chr11-33906826;