1-212075594-T-C

Variant names:

• chr1-212075594-T-C
• rs2014029
• NM_016448.4:c.1036-2579T>C

Variant summary

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

The NM_016448.4(DTL):​c.1036-2579T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0714 in 152,214 control chromosomes in the GnomAD database, including 1,120 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 0.071 (1120 hom., cov: 32)
• Consequence: DTL NM_016448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.521 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTL	NM_016448.4	c.1036-2579T>C		intron_variant	Intron 11 of 14	ENST00000366991.5	NP_057532.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTL	ENST00000366991.5	c.1036-2579T>C		intron_variant	Intron 11 of 14	1	NM_016448.4	ENSP00000355958.4
DTL	ENST00000542077.5	c.910-2579T>C		intron_variant	Intron 10 of 13	2		ENSP00000443870.1
DTL	ENST00000475419.5	n.851-2579T>C		intron_variant	Intron 9 of 12	2
DTL	ENST00000489149.1	n.141-2579T>C		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0714 AC: 10867 AN: 152094 Hom.: 1115 Cov.: 32

Gnomad AFR AF: 0.0176

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.0582

Gnomad EAS AF: 0.538

Gnomad SAS AF: 0.0720

Gnomad FIN AF: 0.0515

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0513

Gnomad OTH AF: 0.0825

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

GnomAD4 genome AF: 0.0714 AC: 10875 AN: 152214 Hom.: 1120 Cov.: 32 AF XY: 0.0758 AC XY: 5641 AN XY: 74438

Gnomad4 AFR AF: 0.0176

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.0582

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.0720

Gnomad4 FIN AF: 0.0515

Gnomad4 NFE AF: 0.0513

Gnomad4 OTH AF: 0.0830

Alfa AF: 0.0644 Hom.: 125

Bravo AF: 0.0846

Asia WGS AF: 0.248 AC: 861 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	11
DANN	Benign	0.83

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: rs2014029; hg19: chr1-212248936;