NM_005574.4:c.-272+3414G>T

Variant names:

• chr11-33878410-C-A
• rs3758638
• NM_005574.4:c.-272+3414G>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.-272+3414G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,022 control chromosomes in the GnomAD database, including 7,944 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 0.31 (7944 hom., cov: 32)
• Consequence: LMO2 NM_005574.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.750
• Publications: 6 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=-0.53).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4	c.-272+3414G>T		intron_variant	Intron 2 of 5	ENST00000257818.3	NP_005565.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3	c.-272+3414G>T		intron_variant	Intron 2 of 5	1	NM_005574.4	ENSP00000257818.2

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46327 AN: 151904 Hom.: 7927 Cov.: 32

Gnomad AFR AF: 0.462

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.345

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.299

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

GnomAD4 genome AF: 0.305 AC: 46367 AN: 152022 Hom.: 7944 Cov.: 32 AF XY: 0.308 AC XY: 22924 AN XY: 74310

African (AFR) AF: 0.462 AC: 19159 AN: 41434

American (AMR) AF: 0.251 AC: 3844 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 860 AN: 3472

East Asian (EAS) AF: 0.406 AC: 2093 AN: 5158

South Asian (SAS) AF: 0.345 AC: 1661 AN: 4814

European-Finnish (FIN) AF: 0.238 AC: 2511 AN: 10552

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15312 AN: 67982

Other (OTH) AF: 0.295 AC: 623 AN: 2110

Alfa AF: 0.251 Hom.: 8603

Bravo AF: 0.312

Asia WGS AF: 0.383 AC: 1330 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.65
PhyloP100		0.75
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: rs3758638; hg19: chr11-33899956;