rs2066575

Variant names:

• chr13-50082446-T-A
• rs2066575
• ENST00000461527.7:n.276T>A

Your query was ambiguous. Multiple possible variants found:

• chr13-50082446-T-A
• chr13-50082446-T-C
• chr13-50082446-T-G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300
• Publications: 17 publications found

Genes affected

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

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]

ENSG00000276089 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLEU1	NR_002605.2	n.278T>A		non_coding_transcript_exon_variant	Exon 1 of 2
DLEU1	NR_109973.1	n.278T>A		non_coding_transcript_exon_variant	Exon 1 of 3
DLEU1	NR_109974.1	n.278T>A		non_coding_transcript_exon_variant	Exon 1 of 7
DLEU2	NR_152566.1	n.241-6793A>T		intron_variant	Intron 1 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLEU1	ENST00000461527.7	n.276T>A		non_coding_transcript_exon_variant	Exon 1 of 6	1
DLEU1	ENST00000463474.7	n.276T>A		non_coding_transcript_exon_variant	Exon 1 of 6	1
DLEU1	ENST00000468168.6	n.276T>A		non_coding_transcript_exon_variant	Exon 1 of 6	1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30126 AN: 152076 Hom.: 3599 Cov.: 32

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

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.: 0 AF XY: 0.212 AC XY: 38249 AN XY: 180048

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

GnomAD4 genome AF: 0.198 AC: 30141 AN: 152194 Hom.: 3597 Cov.: 32 AF XY: 0.197 AC XY: 14679 AN XY: 74414

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: 53 AN: 294

European-Non Finnish (NFE) AF: 0.255 AC: 17354 AN: 67980

Other (OTH) AF: 0.187 AC: 395 AN: 2110

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	4.9
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)

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: rs2066575; hg19: chr13-50656582; COSMIC: COSV52400674;