rs11212495

Positions:

• chr11-108048172-A-G
• chr11-108048172-A-T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.82).
• 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/exons	MANE	Protein	UniProt
CUL5	NM_003478.6	c.235-1718A>G		intron_variant		ENST00000393094.7	NP_003469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL5	ENST00000393094.7	c.235-1718A>G		intron_variant		1	NM_003478.6	ENSP00000376808	P1
CUL5	ENST00000531427.5	c.235-1718A>G		intron_variant, NMD_transcript_variant		1		ENSP00000435376
CUL5	ENST00000532782.1	c.100+1803A>G		intron_variant		3		ENSP00000431221
CUL5	ENST00000532064.5	c.135-1718A>G		intron_variant, NMD_transcript_variant		5		ENSP00000436494

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

Gnomad4 AFR AF: 0.0512

Gnomad4 AMR AF: 0.0881

Gnomad4 ASJ AF: 0.0894

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.0362

Gnomad4 FIN AF: 0.0629

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.0871

Alfa AF: 0.0963 Hom.: 1005

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

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: rs11212495; hg19: chr11-107918899;