rs10863936

Variant names:

• chr1-212064456-G-A
• rs10863936
• NM_016448.4:c.527-461G>A

Variant summary

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

The ENST00000366991.5(DTL):​c.527-461G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 151,962 control chromosomes in the GnomAD database, including 27,406 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 0.59 (27406 hom., cov: 32)
• Consequence: DTL ENST00000366991.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 43 publications found

Genes affected

DTL (HGNC:30288): (denticleless E3 ubiquitin protein ligase homolog) Contributes to ubiquitin-protein transferase activity. Involved in several processes, including protein ubiquitination; regulation of G2/M transition of mitotic cell cycle; and translesion synthesis. Located in centrosome; cytosol; and nuclear lumen. Part of Cul4A-RING E3 ubiquitin ligase complex and Cul4B-RING E3 ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000366991.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTL	NM_016448.4	MANE Select	c.527-461G>A		intron	N/A	NP_057532.4
	DTL	NM_001286230.2		c.401-461G>A		intron	N/A	NP_001273159.2
	DTL	NM_001286229.2		c.-183-461G>A		intron	N/A	NP_001273158.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTL	ENST00000366991.5	TSL:1 MANE Select	c.527-461G>A		intron	N/A	ENSP00000355958.4
	DTL	ENST00000542077.5	TSL:2	c.401-461G>A		intron	N/A	ENSP00000443870.1
	DTL	ENST00000475419.5	TSL:2	n.446-461G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90325 AN: 151844 Hom.: 27375 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.740

Gnomad SAS AF: 0.565

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.525

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.595 AC: 90407 AN: 151962 Hom.: 27406 Cov.: 32 AF XY: 0.596 AC XY: 44235 AN XY: 74282

African (AFR) AF: 0.692 AC: 28678 AN: 41442

American (AMR) AF: 0.664 AC: 10144 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2084 AN: 3470

East Asian (EAS) AF: 0.741 AC: 3829 AN: 5170

South Asian (SAS) AF: 0.564 AC: 2719 AN: 4824

European-Finnish (FIN) AF: 0.512 AC: 5382 AN: 10516

Middle Eastern (MID) AF: 0.531 AC: 156 AN: 294

European-Non Finnish (NFE) AF: 0.525 AC: 35696 AN: 67946

Other (OTH) AF: 0.584 AC: 1231 AN: 2108

Alfa AF: 0.550 Hom.: 94068

Bravo AF: 0.614

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.38
PhyloP100		-0.23
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10863936; hg19: chr1-212237798;