dbSNP rs3740616: LMO2:n.*427A>T (chr11-33859350-T-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000411482.1(LMO2):n.*427A>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.213 in 1,604,886 control chromosomes in the GnomAD database, including 37,846 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 0.18 ( 2734 hom., cov: 32)

Exomes 𝑓: 0.22 ( 35112 hom. )

Consequence

LMO2
ENST00000411482.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.246

Publications

12 publications found

Variant links:

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]

LMO2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.222 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4 link	c.*6A>T		3_prime_UTR_variant	Exon 6 of 6	ENST00000257818.3	NP_005565.2	P25791-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3 link	c.*6A>T		3_prime_UTR_variant	Exon 6 of 6	1	NM_005574.4	ENSP00000257818.2		P25791-3

Frequencies

GnomAD3 genomes

AF:

0.181

AC:

27489

AN:

151980

Hom.:

2732

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.265

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.222

Gnomad EAS

AF:

0.122

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.186

GnomAD2 exomes

AF:

0.189

AC:

47270

AN:

250068

AF XY:

0.194

show subpopulations

Gnomad AFR exome

AF:

0.0999

Gnomad AMR exome

AF:

0.118

Gnomad ASJ exome

AF:

0.221

Gnomad EAS exome

AF:

0.106

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.226

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.217

AC:

315064

AN:

1452788

Hom.:

35112

Cov.:

AF XY:

0.217

AC XY:

156655

AN XY:

722244

show subpopulations

African (AFR)

AF:

0.100

AC:

3334

AN:

33308

American (AMR)

AF:

0.124

AC:

5544

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5785

AN:

26064

East Asian (EAS)

AF:

0.147

AC:

5807

AN:

39588

South Asian (SAS)

AF:

0.180

AC:

15489

AN:

85984

European-Finnish (FIN)

AF:

0.238

AC:

12697

AN:

53366

Middle Eastern (MID)

AF:

0.244

AC:

1377

AN:

5640

European-Non Finnish (NFE)

AF:

0.229

AC:

252676

AN:

1104106

Other (OTH)

AF:

0.206

AC:

12355

AN:

60074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

12458

24915

37373

49830

62288

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8584

17168

25752

34336

42920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.181

AC:

27499

AN:

152098

Hom.:

2734

Cov.:

AF XY:

0.182

AC XY:

13516

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.102

AC:

4214

AN:

41514

American (AMR)

AF:

0.162

AC:

2472

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

771

AN:

3470

East Asian (EAS)

AF:

0.122

AC:

626

AN:

5148

South Asian (SAS)

AF:

0.177

AC:

852

AN:

4814

European-Finnish (FIN)

AF:

0.243

AC:

2568

AN:

10574

Middle Eastern (MID)

AF:

0.266

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.225

AC:

15290

AN:

67982

Other (OTH)

AF:

0.184

AC:

387

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1138

2276

3415

4553

5691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

310

620

930

1240

1550

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.214

Hom.:

1235

Bravo

AF:

0.173

Asia WGS

AF:

0.150

AC:

522

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.44

(source)

DANN

Benign

0.63

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over