chr11-33887000-C-T

Variant names:

• chr11-33887000-C-T
• rs911817
• NM_005574.4:c.-336+4795G>A

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+4795G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.75 in 152,224 control chromosomes in the GnomAD database, including 42,969 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 0.75 (42969 hom., cov: 33)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.74
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4	c.-336+4795G>A		intron_variant	Intron 1 of 5	ENST00000257818.3	NP_005565.2
LMO2	XM_047426944.1	c.-433-4724G>A		intron_variant	Intron 1 of 6		XP_047282900.1
LMO2	XM_017017733.2	c.-265+4795G>A		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+4795G>A		intron_variant	Intron 1 of 5	1	NM_005574.4	ENSP00000257818.2

Frequencies

GnomAD3 genomes AF: 0.750 AC: 114050 AN: 152106 Hom.: 42942 Cov.: 33

Gnomad AFR AF: 0.773

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.667

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.681

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.812

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.754

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.750 AC: 114133 AN: 152224 Hom.: 42969 Cov.: 33 AF XY: 0.747 AC XY: 55602 AN XY: 74414

African (AFR) AF: 0.773 AC: 32103 AN: 41524

American (AMR) AF: 0.667 AC: 10204 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.682 AC: 2367 AN: 3472

East Asian (EAS) AF: 0.681 AC: 3538 AN: 5194

South Asian (SAS) AF: 0.723 AC: 3491 AN: 4830

European-Finnish (FIN) AF: 0.812 AC: 8601 AN: 10590

Middle Eastern (MID) AF: 0.793 AC: 233 AN: 294

European-Non Finnish (NFE) AF: 0.754 AC: 51288 AN: 67996

Other (OTH) AF: 0.726 AC: 1533 AN: 2112

Alfa AF: 0.748 Hom.: 73018

Bravo AF: 0.742

Asia WGS AF: 0.665 AC: 2314 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.18
DANN	Benign	0.51
PhyloP100		-1.7
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: rs911817; hg19: chr11-33908547;