rs3781575

Variant names:

• chr11-33863773-T-C
• rs3781575
• NM_005574.4:c.464+829A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
LMO2	NM_005574.4	c.464+829A>G		intron_variant	Intron 5 of 5	ENST00000257818.3	NP_005565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3	c.464+829A>G		intron_variant	Intron 5 of 5	1	NM_005574.4	ENSP00000257818.2
LMO2	ENST00000395833.7	c.257+829A>G		intron_variant	Intron 2 of 2	1		ENSP00000379175.3
LMO2	ENST00000411482.1	n.*201+829A>G		intron_variant	Intron 2 of 2	1		ENSP00000401967.1
LMO2	ENST00000464025.5	n.550+829A>G		intron_variant	Intron 1 of 1	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

African (AFR) AF: 0.377 AC: 15638 AN: 41482

American (AMR) AF: 0.144 AC: 2195 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0920 AC: 319 AN: 3466

East Asian (EAS) AF: 0.302 AC: 1561 AN: 5176

South Asian (SAS) AF: 0.206 AC: 992 AN: 4820

European-Finnish (FIN) AF: 0.285 AC: 3016 AN: 10574

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11101 AN: 67990

Other (OTH) AF: 0.193 AC: 407 AN: 2112

Alfa AF: 0.172 Hom.: 4340

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
PhyloP100		-1.9
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: rs3781575; hg19: chr11-33885319;