NM_003478.6:c.781-2245G>A

Variant names:

• chr11-108067851-G-A
• rs7104942
• NM_003478.6:c.781-2245G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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=-0.92).
• 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 rank	MANE	Protein	UniProt
CUL5	NM_003478.6	c.781-2245G>A		intron_variant	Intron 7 of 18	ENST00000393094.7	NP_003469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL5	ENST00000393094.7	c.781-2245G>A		intron_variant	Intron 7 of 18	1	NM_003478.6	ENSP00000376808.2
CUL5	ENST00000531427.5	n.781-2245G>A		intron_variant	Intron 7 of 19	1		ENSP00000435376.1

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

African (AFR) AF: 0.570 AC: 23641 AN: 41484

American (AMR) AF: 0.786 AC: 12016 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.786 AC: 2727 AN: 3468

East Asian (EAS) AF: 0.931 AC: 4826 AN: 5186

South Asian (SAS) AF: 0.856 AC: 4130 AN: 4822

European-Finnish (FIN) AF: 0.758 AC: 8021 AN: 10576

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52586 AN: 68000

Other (OTH) AF: 0.763 AC: 1614 AN: 2116

Alfa AF: 0.759 Hom.: 145656

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
PhyloP100		-0.71
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: rs7104942; hg19: chr11-107938578;