rs1060350

chr12-67312686-G-A

Variant summary

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

The NM_018448.5(CAND1):c.3549G>A(p.Leu1183=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,612,692 control chromosomes in the GnomAD database, including 260,499 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 (19270 hom., cov: 32)
  • Exomes 𝑓: 0.57 (241229 hom.)
• Consequence: CAND1 NM_018448.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.843

Genes affected

CAND1 (HGNC:30688): (cullin associated and neddylation dissociated 1) This gene encodes an essential regulator of Cullin-RING ubiquitin ligases, which are in involved in ubiquitinylation of proteins degraded by the Ub proteasome system. The encoded protein binds to unneddylated cullin-RING box protein complexes and acts as an inhibitor of cullin neddylation and of Skp1, cullin, and F box ubiquitin ligase complex assembly and activity. In mammalian cell culture, this protein predominantly localizes to the cytoplasm. Knockdown of this gene in preadipocytes results in blocked adipogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAND1	NM_018448.5	c.3549G>A	p.Leu1183=	synonymous_variant	15/15	ENST00000545606.6
CAND1	NM_001329674.2	c.3477G>A	p.Leu1159=	synonymous_variant	16/16
CAND1	NM_001329675.2	c.3477G>A	p.Leu1159=	synonymous_variant	16/16
CAND1	NM_001329676.2	c.3450G>A	p.Leu1150=	synonymous_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAND1	ENST00000545606.6	c.3549G>A	p.Leu1183=	synonymous_variant	15/15	1	NM_018448.5	P1
CAND1	ENST00000544619.1	c.2169G>A	p.Leu723=	synonymous_variant	9/9	1

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73411 AN: 151812 Hom.: 19251 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.505

GnomAD3 exomes AF: 0.522 AC: 130604 AN: 250100 Hom.: 35403 AF XY: 0.529 AC XY: 71588 AN XY: 135232

Gnomad AFR exome AF: 0.272

Gnomad AMR exome AF: 0.500

Gnomad ASJ exome AF: 0.530

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.521

Gnomad FIN exome AF: 0.538

Gnomad NFE exome AF: 0.590

Gnomad OTH exome AF: 0.538

GnomAD4 exome AF: 0.570 AC: 832364 AN: 1460762 Hom.: 241229 Cov.: 38 AF XY: 0.569 AC XY: 413758 AN XY: 726728

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.315

Gnomad4 SAS exome AF: 0.521

Gnomad4 FIN exome AF: 0.534

Gnomad4 NFE exome AF: 0.598

Gnomad4 OTH exome AF: 0.552

GnomAD4 genome AF: 0.483 AC: 73447 AN: 151930 Hom.: 19270 Cov.: 32 AF XY: 0.482 AC XY: 35788 AN XY: 74202

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.519

Gnomad4 FIN AF: 0.539

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.511

Alfa AF: 0.567 Hom.: 39829

Bravo AF: 0.468

Asia WGS AF: 0.445 AC: 1544 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
Cadd	Benign	6.7
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1060350; hg19: chr12-67706466; COSMIC: COSV73389559; COSMIC: COSV73389559;