rs7103534

Positions:

• chr11-108040925-T-C

Variant summary

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

The NM_003478.6(CUL5):​c.135-5345T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,250 control chromosomes in the GnomAD database, including 1,411 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 0.13 (1411 hom., cov: 32)
• Consequence: CUL5 NM_003478.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.283

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL5	NM_003478.6	c.135-5345T>C		intron_variant		ENST00000393094.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL5	ENST00000393094.7	c.135-5345T>C		intron_variant		1	NM_003478.6	P1
CUL5	ENST00000531427.5	c.135-5345T>C		intron_variant, NMD_transcript_variant		1
CUL5	ENST00000532064.5	c.134+7014T>C		intron_variant, NMD_transcript_variant		5
CUL5	ENST00000526303.1	n.528-5345T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20059 AN: 152132 Hom.: 1404 Cov.: 32

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0862

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.0316

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.132 AC: 20074 AN: 152250 Hom.: 1411 Cov.: 32 AF XY: 0.130 AC XY: 9684 AN XY: 74450

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0860

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.0315

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.124

Gnomad4 OTH AF: 0.119

Alfa AF: 0.122 Hom.: 1898

Bravo AF: 0.132

Asia WGS AF: 0.0840 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.8
DANN	Benign	0.46

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: rs7103534; hg19: chr11-107911652;