11-108046360-A-G

Variant names:

• chr11-108046360-A-G
• rs7117111
• NM_003478.6:c.225A>G

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_003478.6(CUL5):​c.225A>G​(p.Gln75Gln) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.34
• Publications: 23 publications found

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

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

• BP4: Computational evidence support a benign effect (REVEL=0.069).
• 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
CUL5	NM_003478.6	c.225A>G	p.Gln75Gln	synonymous_variant	Exon 3 of 19	ENST00000393094.7	NP_003469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL5	ENST00000393094.7	c.225A>G	p.Gln75Gln	synonymous_variant	Exon 3 of 19	1	NM_003478.6	ENSP00000376808.2

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

GnomAD2 exomes AF: 0.676 AC: 168608 AN: 249538 AF XY: 0.678

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 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

African (AFR) AF: 0.386 AC: 12799 AN: 33184

American (AMR) AF: 0.742 AC: 32769 AN: 44154

Ashkenazi Jewish (ASJ) AF: 0.666 AC: 17296 AN: 25978

East Asian (EAS) AF: 0.900 AC: 35522 AN: 39476

South Asian (SAS) AF: 0.714 AC: 61054 AN: 85552

European-Finnish (FIN) AF: 0.637 AC: 33950 AN: 53328

Middle Eastern (MID) AF: 0.647 AC: 3698 AN: 5718

European-Non Finnish (NFE) AF: 0.646 AC: 708918 AN: 1098106

Other (OTH) AF: 0.653 AC: 39034 AN: 59790

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

African (AFR) AF: 0.400 AC: 16582 AN: 41486

American (AMR) AF: 0.703 AC: 10750 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2313 AN: 3470

East Asian (EAS) AF: 0.899 AC: 4667 AN: 5192

South Asian (SAS) AF: 0.724 AC: 3487 AN: 4818

European-Finnish (FIN) AF: 0.645 AC: 6819 AN: 10572

Middle Eastern (MID) AF: 0.690 AC: 203 AN: 294

European-Non Finnish (NFE) AF: 0.650 AC: 44189 AN: 67986

Other (OTH) AF: 0.643 AC: 1356 AN: 2110

Alfa AF: 0.639 Hom.: 138890

Bravo AF: 0.592

Asia WGS AF: 0.781 AC: 2712 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 29, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.67
PhyloP100		4.3
PromoterAI		0.011	Neutral
Mutation Taster		=96/4	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7117111; hg19: chr11-107917087; COSMIC: COSV108238320;