rs3758638

chr11-33878410-C-Achr11-33878410-C-G

Variant summary

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

The NM_005574.4(LMO2):c.-272+3414G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,022 control chromosomes in the GnomAD database, including 7,944 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 0.31 (7944 hom., cov: 32)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750

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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.-272+3414G>T		intron_variant		ENST00000257818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.-272+3414G>T		intron_variant		1	NM_005574.4

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46327 AN: 151904 Hom.: 7927 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.305 AC: 46367 AN: 152022 Hom.: 7944 Cov.: 32 AF XY: 0.308 AC XY: 22924 AN XY: 74310

Gnomad4 AFR AF: 0.462

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.248

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.238

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.295

Alfa AF: 0.244 Hom.: 6338

Bravo AF: 0.312

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	18
Dann	Benign	0.65

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3758638; hg19: chr11-33899956;