Genetic Variant DLEU1:n.276T>A (chr13-50082446-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The ENST00000461527.7(DLEU1):n.276T>A 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 470,932 control chromosomes in the GnomAD database, including 11,976 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 0.20 ( 3597 hom., cov: 32)

Exomes 𝑓: 0.22 ( 8379 hom. )

Consequence

DLEU1
ENST00000461527.7 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0300

Publications

17 publications found

Variant links:

COSMIC-nc: COSV52400674

Genes affected

DLEU1 (HGNC:13747): (deleted in lymphocytic leukemia 1)

DLEU1 links:

DLEU2 (HGNC:13748): (deleted in lymphocytic leukemia 2) This locus represents a microRNA host gene and also produces long alternatively spliced non-coding RNAs. This genome region was observed to be deleted or epigenetically suppressed in leukemia, and was implicated as a negative regulator of cell proliferation. However, an alternative transcript produced at this locus was also found to promote progression through the cell cycle via angiotensin I converting enzyme 2 and cyclin D1. [provided by RefSeq, Dec 2017]

DLEU2 links:

ENSG00000276089 (HGNC:):

ENSG00000276089 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000461527.7, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.072).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000461527.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank
DLEU1	NR_002605.2	n.278T>A	non_coding_transcript_exon	Exon 1 of 2
DLEU1	NR_109973.1	n.278T>A	non_coding_transcript_exon	Exon 1 of 3
DLEU1	NR_109974.1	n.278T>A	non_coding_transcript_exon	Exon 1 of 7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
DLEU1	ENST00000461527.7	TSL:1	n.276T>A	non_coding_transcript_exon	Exon 1 of 6
DLEU1	ENST00000463474.7	TSL:1	n.276T>A	non_coding_transcript_exon	Exon 1 of 6
DLEU1	ENST00000468168.6	TSL:1	n.276T>A	non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30126

AN:

152076

Hom.:

3599

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0789

Gnomad AMI

AF:

0.423

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.214

Gnomad EAS

AF:

0.337

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.255

Gnomad OTH

AF:

0.185

GnomAD2 exomes

AF:

0.219

AC:

33250

AN:

151586

AF XY:

0.216

show subpopulations

Gnomad AFR exome

AF:

0.0741

Gnomad AMR exome

AF:

0.204

Gnomad ASJ exome

AF:

0.211

Gnomad EAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.250

Gnomad NFE exome

AF:

0.253

Gnomad OTH exome

AF:

0.211

GnomAD4 exome

AF:

0.220

AC:

69964

AN:

318738

Hom.:

8379

Cov.:

AF XY:

0.212

AC XY:

38249

AN XY:

180048

show subpopulations

African (AFR)

AF:

0.0810

AC:

699

AN:

8632

American (AMR)

AF:

0.203

AC:

5533

AN:

27276

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

2309

AN:

10788

East Asian (EAS)

AF:

0.350

AC:

3220

AN:

9212

South Asian (SAS)

AF:

0.120

AC:

7150

AN:

59740

European-Finnish (FIN)

AF:

0.252

AC:

6832

AN:

27066

Middle Eastern (MID)

AF:

0.175

AC:

487

AN:

2784

European-Non Finnish (NFE)

AF:

0.255

AC:

40535

AN:

158918

Other (OTH)

AF:

0.223

AC:

3199

AN:

14322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

3098

6196

9294

12392

15490

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

236

472

708

944

1180

<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:

0.198

AC:

30141

AN:

152194

Hom.:

3597

Cov.:

AF XY:

0.197

AC XY:

14679

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0790

AC:

3281

AN:

41548

American (AMR)

AF:

0.191

AC:

2925

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.214

AC:

741

AN:

3468

East Asian (EAS)

AF:

0.337

AC:

1744

AN:

5170

South Asian (SAS)

AF:

0.118

AC:

570

AN:

4830

European-Finnish (FIN)

AF:

0.254

AC:

2692

AN:

10594

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.255

AC:

17354

AN:

67980

Other (OTH)

AF:

0.187

AC:

395

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1194

2388

3581

4775

5969

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.162

Hom.:

494

Bravo

AF:

0.193

Asia WGS

AF:

0.209

AC:

724

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

4.9

(source)

DANN

Benign

0.78

PhyloP100

0.030

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over