rs4859147

Positions:

• chr3-182964065-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020640.4(DCUN1D1):​c.221-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 1,596,022 control chromosomes in the GnomAD database, including 317,861 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 0.48 (22229 hom., cov: 32)
  • Exomes 𝑓: 0.63 (295632 hom.)
• Consequence: DCUN1D1 NM_020640.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.113

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCUN1D1	NM_020640.4	c.221-16A>G		intron_variant		ENST00000292782.9	NP_065691.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCUN1D1	ENST00000292782.9	c.221-16A>G		intron_variant		1	NM_020640.4	ENSP00000292782.4

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73645 AN: 151966 Hom.: 22244 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.556

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.552

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.500

GnomAD3 exomes AF: 0.559 AC: 138052 AN: 247146 Hom.: 41808 AF XY: 0.569 AC XY: 76050 AN XY: 133666

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.496

Gnomad EAS exome AF: 0.257

Gnomad SAS exome AF: 0.551

Gnomad FIN exome AF: 0.675

Gnomad NFE exome AF: 0.655

Gnomad OTH exome AF: 0.577

GnomAD4 exome AF: 0.627 AC: 905798 AN: 1443940 Hom.: 295632 Cov.: 26 AF XY: 0.627 AC XY: 450128 AN XY: 718272

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.565

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.673

Gnomad4 NFE exome AF: 0.670

Gnomad4 OTH exome AF: 0.587

GnomAD4 genome AF: 0.484 AC: 73606 AN: 152082 Hom.: 22229 Cov.: 32 AF XY: 0.485 AC XY: 36040 AN XY: 74372

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.555

Gnomad4 ASJ AF: 0.487

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.552

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.494

Alfa AF: 0.612 Hom.: 10080

Bravo AF: 0.457

Asia WGS AF: 0.359 AC: 1251 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.71
DANN	Benign	0.37

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: rs4859147; hg19: chr3-182681853; COSMIC: COSV53043482;