NM_003478.6:c.135-5345T>C

Variant names:

• chr11-108040925-T-C
• rs7103534
• NM_003478.6:c.135-5345T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.93).
• 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 rank	MANE	Protein	UniProt
CUL5	NM_003478.6	c.135-5345T>C		intron_variant	Intron 2 of 18	ENST00000393094.7	NP_003469.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CUL5	ENST00000393094.7	c.135-5345T>C		intron_variant	Intron 2 of 18	1	NM_003478.6	ENSP00000376808.2
CUL5	ENST00000531427.5	n.135-5345T>C		intron_variant	Intron 2 of 19	1		ENSP00000435376.1
CUL5	ENST00000526303.1	n.528-5345T>C		intron_variant	Intron 2 of 2	2
CUL5	ENST00000532064.5	n.134+7014T>C		intron_variant	Intron 2 of 5	5		ENSP00000436494.1

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

African (AFR) AF: 0.182 AC: 7551 AN: 41544

American (AMR) AF: 0.0860 AC: 1316 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3468

East Asian (EAS) AF: 0.0315 AC: 163 AN: 5180

South Asian (SAS) AF: 0.133 AC: 642 AN: 4812

European-Finnish (FIN) AF: 0.114 AC: 1209 AN: 10610

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.124 AC: 8451 AN: 68014

Other (OTH) AF: 0.119 AC: 251 AN: 2114

Alfa AF: 0.126 Hom.: 2986

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
PhyloP100		-0.28
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: rs7103534; hg19: chr11-107911652;