rs746481

Variant names:

• chr11-33883825-G-A
• rs746481
• NM_005574.4:c.-335-1938C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-33883825-G-A
• chr11-33883825-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005574.4(LMO2):​c.-335-1938C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.803 in 152,160 control chromosomes in the GnomAD database, including 49,834 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 0.80 (49834 hom., cov: 31)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.772
• Publications: 2 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4	c.-335-1938C>T		intron_variant	Intron 1 of 5	ENST00000257818.3	NP_005565.2
LMO2	XM_047426944.1	c.-433-1549C>T		intron_variant	Intron 1 of 6		XP_047282900.1
LMO2	XM_017017733.2	c.-264-1938C>T		intron_variant	Intron 1 of 4		XP_016873222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3	c.-335-1938C>T		intron_variant	Intron 1 of 5	1	NM_005574.4	ENSP00000257818.2

Frequencies

GnomAD3 genomes AF: 0.803 AC: 122107 AN: 152042 Hom.: 49772 Cov.: 31

Gnomad AFR AF: 0.930

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.673

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.746

Gnomad MID AF: 0.712

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.771

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

GnomAD4 genome AF: 0.803 AC: 122228 AN: 152160 Hom.: 49834 Cov.: 31 AF XY: 0.809 AC XY: 60152 AN XY: 74392

African (AFR) AF: 0.930 AC: 38608 AN: 41530

American (AMR) AF: 0.804 AC: 12283 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.673 AC: 2337 AN: 3470

East Asian (EAS) AF: 0.998 AC: 5170 AN: 5178

South Asian (SAS) AF: 0.859 AC: 4139 AN: 4820

European-Finnish (FIN) AF: 0.746 AC: 7884 AN: 10572

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49238 AN: 67990

Other (OTH) AF: 0.775 AC: 1636 AN: 2112

Alfa AF: 0.746 Hom.: 21827

Bravo AF: 0.814

Asia WGS AF: 0.938 AC: 3259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.50
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs746481; hg19: chr11-33905371;