rs7104942

Positions:

• chr11-108067851-G-A
• chr11-108067851-G-C
• chr11-108067851-G-T

Variant summary

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

The NM_003478.6(CUL5):​c.781-2245G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 152,142 control chromosomes in the GnomAD database, including 40,918 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 0.73 (40918 hom., cov: 33)
• Consequence: CUL5 NM_003478.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.711

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.909 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CUL5	NM_003478.6	c.781-2245G>A		intron_variant		ENST00000393094.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CUL5	ENST00000393094.7	c.781-2245G>A		intron_variant		1	NM_003478.6	P1
CUL5	ENST00000531427.5	c.781-2245G>A		intron_variant, NMD_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.726 AC: 110336 AN: 152024 Hom.: 40895 Cov.: 33

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.681

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.786

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.857

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.760

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

GnomAD4 genome AF: 0.726 AC: 110411 AN: 152142 Hom.: 40918 Cov.: 33 AF XY: 0.731 AC XY: 54348 AN XY: 74364

Gnomad4 AFR AF: 0.570

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.786

Gnomad4 EAS AF: 0.931

Gnomad4 SAS AF: 0.856

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.763

Alfa AF: 0.770 Hom.: 89409

Bravo AF: 0.720

Asia WGS AF: 0.866 AC: 3013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.057
DANN	Benign	0.17

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: rs7104942; hg19: chr11-107938578;