1-212064456-G-A

Position:

• chr1-212064456-G-A

Variant summary

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

The NM_016448.4(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 NM_016448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228

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]

DTL (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTL	NM_016448.4	c.527-461G>A		intron_variant		ENST00000366991.5	NP_057532.4
DTL	NM_001286230.2	c.401-461G>A		intron_variant			NP_001273159.2
DTL	NM_001286229.2	c.-183-461G>A		intron_variant			NP_001273158.2
DTL	XM_011509614.2	c.341-461G>A		intron_variant			XP_011507916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTL	ENST00000366991.5	c.527-461G>A		intron_variant		1	NM_016448.4	ENSP00000355958.4
DTL	ENST00000542077.5	c.401-461G>A		intron_variant		2		ENSP00000443870.1
DTL	ENST00000475419.5	n.446-461G>A		intron_variant		2

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

Gnomad4 AFR AF: 0.692

Gnomad4 AMR AF: 0.664

Gnomad4 ASJ AF: 0.601

Gnomad4 EAS AF: 0.741

Gnomad4 SAS AF: 0.564

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.525

Gnomad4 OTH AF: 0.584

Alfa AF: 0.545 Hom.: 48191

Bravo AF: 0.614

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.38
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs10863936; hg19: chr1-212237798;