1-212036265-A-G

Variant names:

• chr1-212036265-A-G
• rs17018375
• NM_016448.4:c.52+323A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.8).
• 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 57 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTL	NM_016448.4	c.52+323A>G		intron_variant	Intron 1 of 14	ENST00000366991.5	NP_057532.4
DTL	NM_001286230.2	c.52+323A>G		intron_variant	Intron 1 of 13		NP_001273159.2
DTL	NM_001286229.2	c.-532+323A>G		intron_variant	Intron 1 of 12		NP_001273158.2
DTL	XM_011509614.2	c.-135+200A>G		intron_variant	Intron 1 of 14		XP_011507916.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTL	ENST00000366991.5	c.52+323A>G		intron_variant	Intron 1 of 14	1	NM_016448.4	ENSP00000355958.4
DTL	ENST00000542077.5	c.52+323A>G		intron_variant	Intron 1 of 13	2		ENSP00000443870.1
DTL	ENST00000475419.5	n.97+323A>G		intron_variant	Intron 1 of 12	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

African (AFR) AF: 0.0457 AC: 1898 AN: 41494

American (AMR) AF: 0.0201 AC: 308 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3468

East Asian (EAS) AF: 0.000965 AC: 5 AN: 5180

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4824

European-Finnish (FIN) AF: 0.0217 AC: 230 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0206 AC: 1404 AN: 67994

Other (OTH) AF: 0.0194 AC: 41 AN: 2108

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
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism

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: rs17018375; hg19: chr1-212209607;