11-33890901-T-G

Variant names:

• chr11-33890901-T-G
• rs10836129
• NM_005574.4:c.-336+894A>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.-336+894A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 152,004 control chromosomes in the GnomAD database, including 16,032 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 0.45 (16032 hom., cov: 31)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4	c.-336+894A>C		intron_variant	Intron 1 of 5	ENST00000257818.3	NP_005565.2
LMO2	XM_047426944.1	c.-434+894A>C		intron_variant	Intron 1 of 6		XP_047282900.1
LMO2	XM_017017733.2	c.-265+894A>C		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.-336+894A>C		intron_variant	Intron 1 of 5	1	NM_005574.4	ENSP00000257818.2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69091 AN: 151886 Hom.: 16040 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.592

Gnomad AMR AF: 0.433

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.541

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.486

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.455 AC: 69107 AN: 152004 Hom.: 16032 Cov.: 31 AF XY: 0.458 AC XY: 34017 AN XY: 74294

African (AFR) AF: 0.370 AC: 15316 AN: 41444

American (AMR) AF: 0.432 AC: 6604 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1472 AN: 3470

East Asian (EAS) AF: 0.580 AC: 2998 AN: 5166

South Asian (SAS) AF: 0.482 AC: 2324 AN: 4820

European-Finnish (FIN) AF: 0.541 AC: 5700 AN: 10528

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.486 AC: 33039 AN: 67984

Other (OTH) AF: 0.460 AC: 969 AN: 2106

Alfa AF: 0.461 Hom.: 2032

Bravo AF: 0.446

Asia WGS AF: 0.472 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		-0.20
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: rs10836129; hg19: chr11-33912448;