rs17018375

chr1-212036265-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_016448.4(DTL):c.52+323A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.026 in 152,158 control chromosomes in the GnomAD database, including 57 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 0.026 (57 hom., cov: 32)
• Consequence: DTL NM_016448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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=-0.8).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.026 (3954/152158) while in subpopulation AFR AF= 0.0457 (1898/41494). AF 95% confidence interval is 0.044. There are 57 homozygotes in gnomad4. There are 1845 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 56 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTL	NM_016448.4	c.52+323A>G		intron_variant		ENST00000366991.5
DTL	NM_001286229.2	c.-532+323A>G		intron_variant
DTL	NM_001286230.2	c.52+323A>G		intron_variant
DTL	XM_011509614.2	c.-135+200A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTL	ENST00000366991.5	c.52+323A>G		intron_variant		1	NM_016448.4	P1
DTL	ENST00000542077.5	c.52+323A>G		intron_variant		2
DTL	ENST00000475419.5	n.97+323A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3941 AN: 152040 Hom.: 56 Cov.: 32

Gnomad AFR AF: 0.0457

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0202

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0206

Gnomad OTH AF: 0.0177

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

GnomAD4 genome AF: 0.0260 AC: 3954 AN: 152158 Hom.: 57 Cov.: 32 AF XY: 0.0248 AC XY: 1845 AN XY: 74406

Gnomad4 AFR AF: 0.0457

Gnomad4 AMR AF: 0.0201

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.000965

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.0206

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0272 Hom.: 18

Bravo AF: 0.0261

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.82
Dann	Benign	0.56

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: rs17018375; hg19: chr1-212209607;