chr3-182965756-A-G

Variant names:

• chr3-182965756-A-G
• rs143412605
• NM_020640.4:c.4-3T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_020640.4(DCUN1D1):​c.4-3T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00107 in 1,599,378 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00099 (18 hom.)
• Consequence: DCUN1D1 NM_020640.4 splice_region, intron
• Scores: Splicing: ADA: 0.00001531
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.23
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 3-182965756-A-G is Benign according to our data. Variant chr3-182965756-A-G is described in ClinVar as Benign. ClinVar VariationId is 769618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAdExome4 allele frequency = 0.000988 (1430/1447042) while in subpopulation AMR AF = 0.0175 (765/43698). AF 95% confidence interval is 0.0165. There are 18 homozygotes in GnomAdExome4. There are 609 alleles in the male GnomAdExome4 subpopulation. Median coverage is 28. This position passed quality control check.
• BS2: High AC in GnomAd4 at 276 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020640.4. 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
	DCUN1D1	NM_020640.4	MANE Select	c.4-3T>C		splice_region intron	N/A	NP_065691.2
	DCUN1D1	NM_001308101.2		c.-42-3T>C		splice_region intron	N/A	NP_001295030.1	C9JVE2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCUN1D1	ENST00000292782.9	TSL:1 MANE Select	c.4-3T>C		splice_region intron	N/A	ENSP00000292782.4	Q96GG9
	DCUN1D1	ENST00000632685.1	TSL:1	c.-42-3T>C		splice_region intron	N/A	ENSP00000488427.1	C9JVE2
	DCUN1D1	ENST00000925548.1		c.4-3T>C		splice_region intron	N/A	ENSP00000595607.1

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 277 AN: 152218 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000916

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0132

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00558

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00268 AC: 662 AN: 247296 AF XY: 0.00208

Gnomad AFR exome AF: 0.00133

Gnomad AMR exome AF: 0.0159

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00477

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000891

Gnomad OTH exome AF: 0.00317

GnomAD4 exome AF: 0.000988 AC: 1430 AN: 1447042 Hom.: 18 Cov.: 28 AF XY: 0.000846 AC XY: 609 AN XY: 719902

African (AFR) AF: 0.000639 AC: 21 AN: 32884

American (AMR) AF: 0.0175 AC: 765 AN: 43698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.0145 AC: 572 AN: 39472

South Asian (SAS) AF: 0.0000234 AC: 2 AN: 85632

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5222

European-Non Finnish (NFE) AF: 0.0000173 AC: 19 AN: 1101304

Other (OTH) AF: 0.000854 AC: 51 AN: 59748

GnomAD4 genome AF: 0.00181 AC: 276 AN: 152336 Hom.: 3 Cov.: 32 AF XY: 0.00184 AC XY: 137 AN XY: 74496

African (AFR) AF: 0.000914 AC: 38 AN: 41586

American (AMR) AF: 0.0131 AC: 201 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00559 AC: 29 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68028

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.000754 Hom.: 0

Bravo AF: 0.00306

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	13
DANN	Benign	0.90
PhyloP100		3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000015
dbscSNV1_RF	Benign	0.0020
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: rs143412605; hg19: chr3-182683544; COSMIC: COSV53045754;