chr15-88543422-A-T

Position:

• chr15-88543422-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001144074.3(DET1):​c.-11+3118T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,064 control chromosomes in the GnomAD database, including 34,643 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 0.67 (34643 hom., cov: 33)
• Consequence: DET1 NM_001144074.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156

Genes affected

DET1 (HGNC:25477): (DET1 partner of COP1 E3 ubiquitin ligase) Enables ubiquitin ligase-substrate adaptor activity and ubiquitin protein ligase binding activity. Involved in positive regulation of proteasomal ubiquitin-dependent protein catabolic process; protein ubiquitination; and protein-containing complex assembly. Part of Cul4A-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000173867 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DET1	NM_001144074.3	c.-11+3118T>A		intron_variant		ENST00000268148.13	NP_001137546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DET1	ENST00000268148.13	c.-11+3118T>A		intron_variant		1	NM_001144074.3	ENSP00000268148.8
ENSG00000173867	ENST00000649547.1	c.-11+1189T>A		intron_variant				ENSP00000497509.1

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102354 AN: 151946 Hom.: 34614 Cov.: 33

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.684

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.694

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.637

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.633

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

GnomAD4 genome AF: 0.674 AC: 102440 AN: 152064 Hom.: 34643 Cov.: 33 AF XY: 0.676 AC XY: 50205 AN XY: 74308

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.650

Gnomad4 ASJ AF: 0.694

Gnomad4 EAS AF: 0.744

Gnomad4 SAS AF: 0.824

Gnomad4 FIN AF: 0.637

Gnomad4 NFE AF: 0.646

Gnomad4 OTH AF: 0.635

Alfa AF: 0.659 Hom.: 4066

Bravo AF: 0.673

Asia WGS AF: 0.785 AC: 2731 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.7
DANN	Benign	0.23

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

LitVar

Other links and lift over

dbSNP: rs9920066; hg19: chr15-89086653;