rs4859146

Positions:

• chr3-182963952-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000292782.9(DCUN1D1):​c.318G>A​(p.Ala106=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,613,228 control chromosomes in the GnomAD database, including 446,850 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 0.73 (41047 hom., cov: 32)
  • Exomes 𝑓: 0.74 (405803 hom.)
• Consequence: DCUN1D1 ENST00000292782.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

Genes affected

DCUN1D1 (HGNC:18184): (defective in cullin neddylation 1 domain containing 1) Enables cullin family protein binding activity. Involved in positive regulation of protein neddylation and regulation of protein ubiquitination. Located in cytosol and nucleoplasm. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=-2.41 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCUN1D1	NM_020640.4	c.318G>A	p.Ala106=	synonymous_variant	3/7	ENST00000292782.9	NP_065691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCUN1D1	ENST00000292782.9	c.318G>A	p.Ala106=	synonymous_variant	3/7	1	NM_020640.4	ENSP00000292782	P1

Frequencies

GnomAD3 genomes AF: 0.728 AC: 110586 AN: 152008 Hom.: 41012 Cov.: 32

Gnomad AFR AF: 0.743

Gnomad AMI AF: 0.852

Gnomad AMR AF: 0.683

Gnomad ASJ AF: 0.631

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.772

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.717

GnomAD3 exomes AF: 0.687 AC: 172491 AN: 251252 Hom.: 61389 AF XY: 0.686 AC XY: 93159 AN XY: 135800

Gnomad AFR exome AF: 0.738

Gnomad AMR exome AF: 0.661

Gnomad ASJ exome AF: 0.634

Gnomad EAS exome AF: 0.286

Gnomad SAS exome AF: 0.614

Gnomad FIN exome AF: 0.770

Gnomad NFE exome AF: 0.759

Gnomad OTH exome AF: 0.698

GnomAD4 exome AF: 0.738 AC: 1078653 AN: 1461102 Hom.: 405803 Cov.: 43 AF XY: 0.735 AC XY: 534010 AN XY: 726910

Gnomad4 AFR exome AF: 0.745

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.636

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.621

Gnomad4 FIN exome AF: 0.770

Gnomad4 NFE exome AF: 0.771

Gnomad4 OTH exome AF: 0.717

GnomAD4 genome AF: 0.727 AC: 110663 AN: 152126 Hom.: 41047 Cov.: 32 AF XY: 0.722 AC XY: 53723 AN XY: 74358

Gnomad4 AFR AF: 0.743

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.631

Gnomad4 EAS AF: 0.263

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.772

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.715

Alfa AF: 0.750 Hom.: 22688

Bravo AF: 0.720

Asia WGS AF: 0.473 AC: 1649 AN: 3478

EpiCase AF: 0.760

EpiControl AF: 0.750

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	5.0
DANN	Benign	0.57

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: rs4859146; hg19: chr3-182681740; COSMIC: COSV53044616; COSMIC: COSV53044616;