rs4007

Variant names:

• chr11-33865996-T-A
• rs4007
• NM_005574.4:c.249-1179A>T

Variant summary

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

The NM_005574.4(LMO2):​c.249-1179A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,142 control chromosomes in the GnomAD database, including 4,214 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 0.22 (4214 hom., cov: 32)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4	c.249-1179A>T		intron_variant	Intron 4 of 5	ENST00000257818.3	NP_005565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3	c.249-1179A>T		intron_variant	Intron 4 of 5	1	NM_005574.4	ENSP00000257818.2
LMO2	ENST00000395833.7	c.42-1179A>T		intron_variant	Intron 1 of 2	1		ENSP00000379175.3
LMO2	ENST00000411482.1	n.42-1067A>T		intron_variant	Intron 1 of 2	1		ENSP00000401967.1
LMO2	ENST00000465614.1	n.816-1179A>T		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33880 AN: 152024 Hom.: 4192 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.181

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.0998

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.193

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.223 AC: 33948 AN: 152142 Hom.: 4214 Cov.: 32 AF XY: 0.224 AC XY: 16642 AN XY: 74384

African (AFR) AF: 0.307 AC: 12752 AN: 41480

American (AMR) AF: 0.151 AC: 2314 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0998 AC: 346 AN: 3468

East Asian (EAS) AF: 0.206 AC: 1066 AN: 5184

South Asian (SAS) AF: 0.103 AC: 499 AN: 4826

European-Finnish (FIN) AF: 0.309 AC: 3271 AN: 10590

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13128 AN: 67980

Other (OTH) AF: 0.187 AC: 393 AN: 2104

Alfa AF: 0.212 Hom.: 448

Bravo AF: 0.217

Asia WGS AF: 0.188 AC: 653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.6
DANN	Benign	0.79
PhyloP100		0.35
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: rs4007; hg19: chr11-33887542;