11-108048172-A-G

Variant names:

• chr11-108048172-A-G
• rs11212495
• NM_003478.6:c.235-1718A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003478.6(CUL5):​c.235-1718A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 151,056 control chromosomes in the GnomAD database, including 608 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 0.085 (608 hom., cov: 32)
• Consequence: CUL5 NM_003478.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20
• Publications: 4 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CUL5	NM_003478.6	c.235-1718A>G		intron_variant	Intron 3 of 18	ENST00000393094.7	NP_003469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL5	ENST00000393094.7	c.235-1718A>G		intron_variant	Intron 3 of 18	1	NM_003478.6	ENSP00000376808.2
CUL5	ENST00000531427.5	n.235-1718A>G		intron_variant	Intron 3 of 19	1		ENSP00000435376.1
CUL5	ENST00000532782.1	c.99+1803A>G		intron_variant	Intron 1 of 2	3		ENSP00000431221.1
CUL5	ENST00000532064.5	n.135-1718A>G		intron_variant	Intron 2 of 5	5		ENSP00000436494.1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12787 AN: 150952 Hom.: 608 Cov.: 32

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0882

Gnomad ASJ AF: 0.0894

Gnomad EAS AF: 0.162

Gnomad SAS AF: 0.0366

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.0845

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0846 AC: 12786 AN: 151056 Hom.: 608 Cov.: 32 AF XY: 0.0822 AC XY: 6058 AN XY: 73680

African (AFR) AF: 0.0512 AC: 2108 AN: 41180

American (AMR) AF: 0.0881 AC: 1340 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.0894 AC: 310 AN: 3468

East Asian (EAS) AF: 0.161 AC: 833 AN: 5168

South Asian (SAS) AF: 0.0362 AC: 173 AN: 4776

European-Finnish (FIN) AF: 0.0629 AC: 639 AN: 10164

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7104 AN: 67790

Other (OTH) AF: 0.0871 AC: 183 AN: 2100

Alfa AF: 0.0977 Hom.: 2335

Bravo AF: 0.0859

Asia WGS AF: 0.110 AC: 382 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.50
PhyloP100		2.2
Mutation Taster		=100/0	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: rs11212495; hg19: chr11-107918899;