rs17018426

Variant names:

• chr1-212068888-C-G
• rs17018426
• NM_016448.4:c.922+185C>G

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BS1_Supporting BS2

The NM_016448.4(DTL):​c.922+185C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 152,268 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency: Genomes: 𝑓 0.026 (58 hom., cov: 32)
• Consequence: DTL NM_016448.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531
• 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0262 (3993/152268) while in subpopulation AFR AF = 0.0465 (1933/41560). AF 95% confidence interval is 0.0448. There are 58 homozygotes in GnomAd4. There are 1871 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016448.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTL	NM_016448.4	MANE Select	c.922+185C>G		intron	N/A	NP_057532.4
	DTL	NM_001286230.2		c.796+185C>G		intron	N/A	NP_001273159.2
	DTL	NM_001286229.2		c.109+185C>G		intron	N/A	NP_001273158.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTL	ENST00000366991.5	TSL:1 MANE Select	c.922+185C>G		intron	N/A	ENSP00000355958.4
	DTL	ENST00000935628.1		c.970+185C>G		intron	N/A	ENSP00000605687.1
	DTL	ENST00000935625.1		c.919+185C>G		intron	N/A	ENSP00000605684.1

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3980 AN: 152152 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0464

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0204

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0218

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: 0.0262 AC: 3993 AN: 152268 Hom.: 58 Cov.: 32 AF XY: 0.0251 AC XY: 1871 AN XY: 74448

African (AFR) AF: 0.0465 AC: 1933 AN: 41560

American (AMR) AF: 0.0203 AC: 311 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.000964 AC: 5 AN: 5188

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4820

European-Finnish (FIN) AF: 0.0218 AC: 231 AN: 10608

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.0206 AC: 1404 AN: 68010

Other (OTH) AF: 0.0194 AC: 41 AN: 2114

Alfa AF: 0.0267 Hom.: 9

Bravo AF: 0.0264

Asia WGS AF: 0.0230 AC: 79 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		0.53
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: rs17018426; hg19: chr1-212242230;