rs3807446

Positions:

• chr7-148770355-T-C

Variant summary

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

The NM_003592.3(CUL1):​c.1083+2606T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0541 in 152,282 control chromosomes in the GnomAD database, including 304 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 0.054 (304 hom., cov: 33)
• Consequence: CUL1 NM_003592.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581

Genes affected

CUL1 (HGNC:2551): (cullin 1) Predicted to enable ubiquitin protein ligase binding activity and ubiquitin-protein transferase activity. Involved in SCF-dependent proteasomal ubiquitin-dependent protein catabolic process and protein ubiquitination. Located in plasma membrane. Part of Parkin-FBXW7-Cul1 ubiquitin ligase complex and SCF 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CUL1	NM_003592.3	c.1083+2606T>C		intron_variant		ENST00000325222.9	NP_003583.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CUL1	ENST00000325222.9	c.1083+2606T>C		intron_variant		1	NM_003592.3	ENSP00000326804.3

Frequencies

GnomAD3 genomes AF: 0.0541 AC: 8233 AN: 152164 Hom.: 300 Cov.: 33

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.0304

Gnomad SAS AF: 0.0438

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0482

Gnomad OTH AF: 0.0532

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

GnomAD4 genome AF: 0.0541 AC: 8237 AN: 152282 Hom.: 304 Cov.: 33 AF XY: 0.0546 AC XY: 4068 AN XY: 74482

Gnomad4 AFR AF: 0.0475

Gnomad4 AMR AF: 0.105

Gnomad4 ASJ AF: 0.0554

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0623

Gnomad4 NFE AF: 0.0482

Gnomad4 OTH AF: 0.0527

Alfa AF: 0.0513 Hom.: 366

Bravo AF: 0.0602

Asia WGS AF: 0.0550 AC: 191 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.73
DANN	Benign	0.41

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: rs3807446; hg19: chr7-148467447;