rs17018426

Variant names:

• chr1-212068888-C-G
• rs17018426
• NM_016448.4:c.922+185C>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.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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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 -12 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.
• BS2: High Homozygotes in GnomAd4 at 58 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTL	NM_016448.4	c.922+185C>G		intron_variant	Intron 10 of 14	ENST00000366991.5	NP_057532.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTL	ENST00000366991.5	c.922+185C>G		intron_variant	Intron 10 of 14	1	NM_016448.4	ENSP00000355958.4
DTL	ENST00000542077.5	c.796+185C>G		intron_variant	Intron 9 of 13	2		ENSP00000443870.1
DTL	ENST00000475419.5	n.737+185C>G		intron_variant	Intron 8 of 12	2

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 v4.3

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;