rs3781575

Positions:

• chr11-33863773-T-C

Variant summary

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

The NM_005574.4(LMO2):​c.464+829A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 152,120 control chromosomes in the GnomAD database, including 4,909 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 0.23 (4909 hom., cov: 33)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LMO2	NM_005574.4	c.464+829A>G		intron_variant		ENST00000257818.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
LMO2	ENST00000257818.3	c.464+829A>G		intron_variant		1	NM_005574.4
LMO2	ENST00000395833.7	c.257+829A>G		intron_variant		1		P1
LMO2	ENST00000411482.1	c.*201+829A>G		intron_variant, NMD_transcript_variant		1
LMO2	ENST00000464025.5	n.550+829A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35336 AN: 152002 Hom.: 4879 Cov.: 33

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.182

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.0920

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.233 AC: 35415 AN: 152120 Hom.: 4909 Cov.: 33 AF XY: 0.237 AC XY: 17597 AN XY: 74380

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.144

Gnomad4 ASJ AF: 0.0920

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.285

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.193

Alfa AF: 0.166 Hom.: 3160

Bravo AF: 0.228

Asia WGS AF: 0.279 AC: 968 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	0.085
DANN	Benign	0.37

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: rs3781575; hg19: chr11-33885319;