11-108046360-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_003478.6(CUL5):c.225A>G(p.Gln75=) variant causes a synonymous change. The variant allele was found at a frequency of 0.649 in 1,597,410 control chromosomes in the GnomAD database, including 341,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.60 (28662 hom., cov: 33)
  • Exomes 𝑓: 0.65 (312729 hom.)
• Consequence: CUL5 NM_003478.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.34

Genes affected

CUL5 (HGNC:2556): (cullin 5) Enables ubiquitin protein ligase binding activity. Predicted to be involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Predicted to act upstream of or within cerebral cortex radially oriented cell migration and radial glia guided migration of Purkinje cell. Located in site of DNA damage. Part of Cul5-RING 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=-0.42).
• BP6: Variant 11-108046360-A-G is Benign according to our data. Variant chr11-108046360-A-G is described in ClinVar as [Benign]. Clinvar id is 1272688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL5	NM_003478.6	c.225A>G	p.Gln75=	synonymous_variant	3/19	ENST00000393094.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL5	ENST00000393094.7	c.225A>G	p.Gln75=	synonymous_variant	3/19	1	NM_003478.6	P1

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90875 AN: 152006 Hom.: 28648 Cov.: 33

Gnomad AFR AF: 0.400

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.724

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.650

Gnomad OTH AF: 0.638

GnomAD3 exomes AF: 0.676 AC: 168608 AN: 249538 Hom.: 58492 AF XY: 0.678 AC XY: 91517 AN XY: 134958

Gnomad AFR exome AF: 0.392

Gnomad AMR exome AF: 0.752

Gnomad ASJ exome AF: 0.658

Gnomad EAS exome AF: 0.898

Gnomad SAS exome AF: 0.714

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.656

Gnomad OTH exome AF: 0.675

GnomAD4 exome AF: 0.654 AC: 945040 AN: 1445286 Hom.: 312729 Cov.: 28 AF XY: 0.656 AC XY: 472542 AN XY: 719950

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.742

Gnomad4 ASJ exome AF: 0.666

Gnomad4 EAS exome AF: 0.900

Gnomad4 SAS exome AF: 0.714

Gnomad4 FIN exome AF: 0.637

Gnomad4 NFE exome AF: 0.646

Gnomad4 OTH exome AF: 0.653

GnomAD4 genome AF: 0.598 AC: 90930 AN: 152124 Hom.: 28662 Cov.: 33 AF XY: 0.605 AC XY: 45002 AN XY: 74376

Gnomad4 AFR AF: 0.400

Gnomad4 AMR AF: 0.703

Gnomad4 ASJ AF: 0.667

Gnomad4 EAS AF: 0.899

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.645

Gnomad4 NFE AF: 0.650

Gnomad4 OTH AF: 0.643

Alfa AF: 0.647 Hom.: 65497

Bravo AF: 0.592

Asia WGS AF: 0.781 AC: 2712 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2020

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
Cadd	Benign	11
Dann	Benign	0.67

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: rs7117111; hg19: chr11-107917087;