rs9535416

Variant names:

• chr13-50050004-G-A
• rs9535416
• ENST00000421758.7:n.347-342C>T

Variant summary

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

The ENST00000421758.7(DLEU2):​n.347-342C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,924 control chromosomes in the GnomAD database, including 12,442 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 0.38 (12442 hom., cov: 32)
• Consequence: DLEU2 ENST00000421758.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.165
• Publications: 15 publications found

Genes affected

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000421758.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLEU2	NR_152566.1		n.577-342C>T		intron	N/A
	DLEU2	NR_152567.1		n.382-342C>T		intron	N/A
	DLEU2	NR_152568.1		n.287-342C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLEU2	ENST00000421758.7	TSL:1	n.347-342C>T		intron	N/A
	DLEU2	ENST00000425586.6	TSL:1	n.582-342C>T		intron	N/A
	DLEU2	ENST00000433070.9	TSL:1	n.315-342C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57533 AN: 151806 Hom.: 12447 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.0118

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.380

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.379 AC: 57526 AN: 151924 Hom.: 12442 Cov.: 32 AF XY: 0.372 AC XY: 27612 AN XY: 74268

African (AFR) AF: 0.214 AC: 8862 AN: 41454

American (AMR) AF: 0.397 AC: 6071 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1465 AN: 3460

East Asian (EAS) AF: 0.0118 AC: 61 AN: 5176

South Asian (SAS) AF: 0.358 AC: 1727 AN: 4822

European-Finnish (FIN) AF: 0.380 AC: 4004 AN: 10534

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.499 AC: 33890 AN: 67886

Other (OTH) AF: 0.417 AC: 878 AN: 2106

Alfa AF: 0.455 Hom.: 51937

Bravo AF: 0.369

Asia WGS AF: 0.225 AC: 788 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.3
DANN	Benign	0.40
PhyloP100		0.17

Splicing

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.

Other links and lift over

dbSNP: rs9535416;

hg19: chr13-50624140;