rs911817

Positions:

• chr11-33887000-C-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.97).
• 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/exons	MANE	Protein	UniProt
LMO2	NM_005574.4	c.-336+4795G>A		intron_variant		ENST00000257818.3	NP_005565.2
LMO2	XM_047426944.1	c.-433-4724G>A		intron_variant			XP_047282900.1
LMO2	XM_017017733.2	c.-265+4795G>A		intron_variant			XP_016873222.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3	c.-336+4795G>A		intron_variant		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

Gnomad4 AFR AF: 0.773

Gnomad4 AMR AF: 0.667

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.723

Gnomad4 FIN AF: 0.812

Gnomad4 NFE AF: 0.754

Gnomad4 OTH AF: 0.726

Alfa AF: 0.748 Hom.: 58103

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs911817; hg19: chr11-33908547;